A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.
Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.
A structurally-related group of signaling proteins that are phosphorylated by the INSULIN RECEPTOR PROTEIN-TYROSINE KINASE. The proteins share in common an N-terminal PHOSPHOLIPID-binding domain, a phosphotyrosine-binding domain that interacts with the phosphorylated INSULIN RECEPTOR, and a C-terminal TYROSINE-rich domain. Upon tyrosine phosphorylation insulin receptor substrate proteins interact with specific SH2 DOMAIN-containing proteins that are involved in insulin receptor signaling.
A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.
Insulin formulations that contain substances that retard absorption thus extending the time period of action.
Antibodies specific to INSULIN.
Substances which lower blood glucose levels.
Compounds which inhibit or antagonize the biosynthesis or action of insulin.
Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.
Insulin that has been modified so that the B-chain contains a LYSINE at position 28 instead of a PROLINE and a PROLINE at position 29 instead of a LYSINE. It is used to manage BLOOD GLUCOSE levels in patients with TYPE 2 DIABETES.
A test to determine the ability of an individual to maintain HOMEOSTASIS of BLOOD GLUCOSE. It includes measuring blood glucose levels in a fasting state, and at prescribed intervals before and after oral glucose intake (75 or 100 g) or intravenous infusion (0.5 g/kg).
A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.
Portable or implantable devices for infusion of insulin. Includes open-loop systems which may be patient-operated or controlled by a pre-set program and are designed for constant delivery of small quantities of insulin, increased during food ingestion, and closed-loop systems which deliver quantities of insulin automatically based on an electronic glucose sensor.
Maintenance of a constant blood glucose level by perfusion or infusion with glucose or insulin. It is used for the study of metabolic rates (e.g., in glucose, lipid, amino acid metabolism) at constant glucose concentration.
Insulin that has been modified to contain an ASPARTIC ACID instead of a PROLINE at position 38 of the B-chain.
An intermediate-acting INSULIN preparation with onset time of 2 hours and duration of 24 hours. It is produced by crystallizing ZINC-insulin-PROTAMINES at neutral pH 7. Thus it is called neutral protamine Hagedorn for inventor Hans Christian Hagedorn.
Regular insulin preparations that contain the SUS SCROFA insulin peptide sequence.
A syndrome with excessively high INSULIN levels in the BLOOD. It may cause HYPOGLYCEMIA. Etiology of hyperinsulinism varies, including hypersecretion of a beta cell tumor (INSULINOMA); autoantibodies against insulin (INSULIN ANTIBODIES); defective insulin receptor (INSULIN RESISTANCE); or overuse of exogenous insulin or HYPOGLYCEMIC AGENTS.
Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white.
A type of pancreatic cell representing about 50-80% of the islet cells. Beta cells secrete INSULIN.
Peptide hormones that cause an increase in the absorption of GLUCOSE by cells within organs such as LIVER, MUSCLE and ADIPOSE TISSUE. During normal metabolism insulins are produced by the PANCREATIC BETA CELLS in response to increased GLUCOSE. Natural and chemically-modified forms of insulin are also used in the treatment of GLUCOSE METABOLISM DISORDERS such as DIABETES MELLITUS.
A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal GLUCAGON-LIKE PEPTIDES. Glucagon is secreted by PANCREATIC ALPHA CELLS and plays an important role in regulation of BLOOD GLUCOSE concentration, ketone metabolism, and several other biochemical and physiological processes. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1511)
A status with BODY WEIGHT that is grossly above the acceptable or desirable weight, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).
Regular insulin preparations that contain the HUMAN insulin peptide sequence.
The middle segment of proinsulin that is between the N-terminal B-chain and the C-terminal A-chain. It is a pancreatic peptide of about 31 residues, depending on the species. Upon proteolytic cleavage of proinsulin, equimolar INSULIN and C-peptide are released. C-peptide immunoassay has been used to assess pancreatic beta cell function in diabetic patients with circulating insulin antibodies or exogenous insulin. Half-life of C-peptide is 30 min, almost 8 times that of insulin.
A pancreatic polypeptide of about 110 amino acids, depending on the species, that is the precursor of insulin. Proinsulin, produced by the PANCREATIC BETA CELLS, is comprised sequentially of the N-terminal B-chain, the proteolytically removable connecting C-peptide, and the C-terminal A-chain. It also contains three disulfide bonds, two between A-chain and B-chain. After cleavage at two locations, insulin and C-peptide are the secreted products. Intact proinsulin with low bioactivity also is secreted in small amounts.
Abstaining from all food.
Glucose in blood.
Abnormally high BLOOD GLUCOSE level.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.
A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
FATTY ACIDS found in the plasma that are complexed with SERUM ALBUMIN for transport. These fatty acids are not in glycerol ester form.
A glucose transport protein found in mature MUSCLE CELLS and ADIPOCYTES. It promotes transport of glucose from the BLOOD into target TISSUES. The inactive form of the protein is localized in CYTOPLASMIC VESICLES. In response to INSULIN, it is translocated to the PLASMA MEMBRANE where it facilitates glucose uptake.
Cells in the body that store FATS, usually in the form of TRIGLYCERIDES. WHITE ADIPOCYTES are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. BROWN ADIPOCYTES are thermogenic cells that can be found in newborns of some species and hibernating mammals.
Insulin derivatives and preparations that are designed to induce a rapid HYPOGLYCEMIC EFFECT.
A syndrome of abnormally low BLOOD GLUCOSE level. Clinical hypoglycemia has diverse etiologies. Severe hypoglycemia eventually lead to glucose deprivation of the CENTRAL NERVOUS SYSTEM resulting in HUNGER; SWEATING; PARESTHESIA; impaired mental function; SEIZURES; COMA; and even DEATH.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY.
A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.
A pathological state in which BLOOD GLUCOSE level is less than approximately 140 mg/100 ml of PLASMA at fasting, and above approximately 200 mg/100 ml plasma at 30-, 60-, or 90-minute during a GLUCOSE TOLERANCE TEST. This condition is seen frequently in DIABETES MELLITUS, but also occurs with other diseases and MALNUTRITION.
A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.
A 16-kDa peptide hormone secreted from WHITE ADIPOCYTES. Leptin serves as a feedback signal from fat cells to the CENTRAL NERVOUS SYSTEM in regulation of food intake, energy balance, and fat storage.
2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity.
The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.
A large group of membrane transport proteins that shuttle MONOSACCHARIDES across CELL MEMBRANES.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
A benign tumor of the PANCREATIC BETA CELLS. Insulinoma secretes excess INSULIN resulting in HYPOGLYCEMIA.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
An insulin preparation that is designed to provide immediate and long term glycemic control in a single dosage. Biphasic insulin typically contains a mixture of REGULAR INSULIN or SHORT-ACTING INSULIN combined with a LONG-ACTING INSULIN.
The rate dynamics in chemical or physical systems.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
Minor hemoglobin components of human erythrocytes designated A1a, A1b, and A1c. Hemoglobin A1c is most important since its sugar moiety is glucose covalently bound to the terminal amino acid of the beta chain. Since normal glycohemoglobin concentrations exclude marked blood glucose fluctuations over the preceding three to four weeks, the concentration of glycosylated hemoglobin A is a more reliable index of the blood sugar average over a long period of time.
The processes whereby the internal environment of an organism tends to remain balanced and stable.
A 30-kDa COMPLEMENT C1Q-related protein, the most abundant gene product secreted by FAT CELLS of the white ADIPOSE TISSUE. Adiponectin modulates several physiological processes, such as metabolism of GLUCOSE and FATTY ACIDS, and immune responses. Decreased plasma adiponectin levels are associated with INSULIN RESISTANCE; TYPE 2 DIABETES MELLITUS; OBESITY; and ATHEROSCLEROSIS.
The time frame after a meal or FOOD INTAKE.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed)
Elements of limited time intervals, contributing to particular results or situations.
A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.
A peptide of 36 or 37 amino acids that is derived from PROGLUCAGON and mainly produced by the INTESTINAL L CELLS. GLP-1(1-37 or 1-36) is further N-terminally truncated resulting in GLP-1(7-37) or GLP-1-(7-36) which can be amidated. These GLP-1 peptides are known to enhance glucose-dependent INSULIN release, suppress GLUCAGON release and gastric emptying, lower BLOOD GLUCOSE, and reduce food intake.
Established cell cultures that have the potential to propagate indefinitely.
An indicator of body density as determined by the relationship of BODY WEIGHT to BODY HEIGHT. BMI=weight (kg)/height squared (m2). BMI correlates with body fat (ADIPOSE TISSUE). Their relationship varies with age and gender. For adults, BMI falls into these categories: below 18.5 (underweight); 18.5-24.9 (normal); 25.0-29.9 (overweight); 30.0 and above (obese). (National Center for Health Statistics, Centers for Disease Control and Prevention)
A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289)
Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Mutant mice exhibiting a marked obesity coupled with overeating, hyperglycemia, hyperinsulinemia, marked insulin resistance, and infertility when in a homozygous state. They may be inbred or hybrid.
Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.
THIAZOLES with two keto oxygens. Members are insulin-sensitizing agents which overcome INSULIN RESISTANCE by activation of the peroxisome proliferator activated receptor gamma (PPAR-gamma).
A continuous cell line that is a substrain of SWISS 3T3 CELLS developed though clonal isolation. The mouse fibroblast cells undergo an adipose-like conversion as they move to a confluent and contact-inhibited state.
The metabolic process of breaking down LIPIDS to release FREE FATTY ACIDS, the major oxidative fuel for the body. Lipolysis may involve dietary lipids in the DIGESTIVE TRACT, circulating lipids in the BLOOD, and stored lipids in the ADIPOSE TISSUE or the LIVER. A number of enzymes are involved in such lipid hydrolysis, such as LIPASE and LIPOPROTEIN LIPASE from various tissues.
The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
A protein-tyrosine kinase receptor that is closely related in structure to the INSULIN RECEPTOR. Although commonly referred to as the IGF-I receptor, it binds both IGF-I and IGF-II with high affinity. It is comprised of a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The beta subunit contains an intrinsic tyrosine kinase domain.
Two populations of Zucker rats have been cited in research--the "fatty" or obese and the lean. The "fatty" rat (Rattus norvegicus) appeared as a spontaneous mutant. The obese condition appears to be due to a single recessive gene.
A cluster of metabolic risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome X include excess ABDOMINAL FAT; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state. (from AHA/NHLBI/ADA Conference Proceedings, Circulation 2004; 109:551-556)
A sulphonylurea hypoglycemic agent with actions and uses similar to those of CHLORPROPAMIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290)
The administration of liquid medication or nutrients under the skin, usually over minutes or hours.
The consumption of edible substances.
Carbohydrates present in food comprising digestible sugars and starches and indigestible cellulose and other dietary fibers. The former are the major source of energy. The sugars are in beet and cane sugar, fruits, honey, sweet corn, corn syrup, milk and milk products, etc.; the starches are in cereal grains, legumes (FABACEAE), tubers, etc. (From Claudio & Lagua, Nutrition and Diet Therapy Dictionary, 3d ed, p32, p277)
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
The relative amounts of various components in the body, such as percentage of body fat.
The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.
Consumption of excessive DIETARY FATS.
The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.
An antibiotic that is produced by Stretomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
The chemical reactions involved in the production and utilization of various forms of energy in cells.
An enzyme that catalyzes the transfer of D-glucose from UDPglucose into 1,4-alpha-D-glucosyl chains. EC
A 14-amino acid peptide named for its ability to inhibit pituitary GROWTH HORMONE release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of THYROID-STIMULATING HORMONE; PROLACTIN; INSULIN; and GLUCAGON besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, SRIF-28 with a 14-amino acid extension at the N-terminal.
The amount of fat or lipid deposit at a site or an organ in the body, an indicator of body fat status.
Biosynthesis of GLUCOSE from nonhexose or non-carbohydrate precursors, such as LACTATE; PYRUVATE; ALANINE; and GLYCEROL.
A non-metabolizable glucose analogue that is not phosphorylated by hexokinase. 3-O-Methylglucose is used as a marker to assess glucose transport by evaluating its uptake within various cells and organ systems. (J Neurochem 1993;60(4):1498-504)
A group of enzymes that catalyzes the conversion of ATP and D-glucose to ADP and D-glucose 6-phosphate. They are found in invertebrates and microorganisms, and are highly specific for glucose. (Enzyme Nomenclature, 1992) EC
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
A polypeptide that is secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Growth hormone, also known as somatotropin, stimulates mitosis, cell differentiation and cell growth. Species-specific growth hormones have been synthesized.
Lipid infiltration of the hepatic parenchymal cells resulting in a yellow-colored liver. The abnormal lipid accumulation is usually in the form of TRIGLYCERIDES, either as a single large droplet or multiple small droplets. Fatty liver is caused by an imbalance in the metabolism of FATTY ACIDS.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin.
A complex disorder characterized by infertility, HIRSUTISM; OBESITY; and various menstrual disturbances such as OLIGOMENORRHEA; AMENORRHEA; ANOVULATION. Polycystic ovary syndrome is usually associated with bilateral enlarged ovaries studded with atretic follicles, not with cysts. The term, polycystic ovary, is misleading.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed)
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various ENDOCRINE GLANDS and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects.
An enzyme the catalyzes the degradation of insulin, glucagon and other polypeptides. It is inhibited by bacitracin, chelating agents EDTA and 1,10-phenanthroline, and by thiol-blocking reagents such as N-ethylmaleimide, but not phosphoramidon. (Eur J Biochem 1994;223:1-5) EC
A monosaccharide in sweet fruits and honey that is soluble in water, alcohol, or ether. It is used as a preservative and an intravenous infusion in parenteral feeding.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
A gastrointestinal peptide hormone of about 43-amino acids. It is found to be a potent stimulator of INSULIN secretion and a relatively poor inhibitor of GASTRIC ACID secretion.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A life-threatening complication of diabetes mellitus, primarily of TYPE 1 DIABETES MELLITUS with severe INSULIN deficiency and extreme HYPERGLYCEMIA. It is characterized by KETOSIS; DEHYDRATION; and depressed consciousness leading to COMA.
The time period before the development of symptomatic diabetes. For example, certain risk factors can be observed in subjects who subsequently develop INSULIN RESISTANCE as in type 2 diabetes (DIABETES MELLITUS, TYPE 2).
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
Contractile tissue that produces movement in animals.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Regular course of eating and drinking adopted by a person or animal.
A subtype of non-receptor protein tyrosine phosphatases that includes two distinctive targeting motifs; an N-terminal motif specific for the INSULIN RECEPTOR, and a C-terminal motif specific for the SH3 domain containing proteins. This subtype includes a hydrophobic domain which localizes it to the ENDOPLASMIC RETICULUM.
A glucose transport facilitator that is expressed primarily in PANCREATIC BETA CELLS; LIVER; and KIDNEYS. It may function as a GLUCOSE sensor to regulate INSULIN release and glucose HOMEOSTASIS.
Studies comparing two or more treatments or interventions in which the subjects or patients, upon completion of the course of one treatment, are switched to another. In the case of two treatments, A and B, half the subjects are randomly allocated to receive these in the order A, B and half to receive them in the order B, A. A criticism of this design is that effects of the first treatment may carry over into the period when the second is given. (Last, A Dictionary of Epidemiology, 2d ed)
The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.
A benzothiadiazine derivative that is a peripheral vasodilator used for hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide group.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.
A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent.
A 12-kDa cysteine-rich polypeptide hormone secreted by FAT CELLS in the ADIPOSE TISSUE. It is the founding member of the resistin-like molecule (RELM) hormone family. Resistin suppresses the ability of INSULIN to stimulate cellular GLUCOSE uptake.
Fatty tissue inside the ABDOMINAL CAVITY, including visceral fat and retroperitoneal fat. It is the most metabolically active fat in the body and easily accessible for LIPOLYSIS. Increased visceral fat is associated with metabolic complications of OBESITY.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.
An essential branched-chain amino acid important for hemoglobin formation.
The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.
Polypeptides produced by the ADIPOCYTES. They include LEPTIN; ADIPONECTIN; RESISTIN; and many cytokines of the immune system, such as TUMOR NECROSIS FACTOR-ALPHA; INTERLEUKIN-6; and COMPLEMENT FACTOR D (also known as ADIPSIN). They have potent autocrine, paracrine, and endocrine functions.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.
The increase in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical.
Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator.
Salts and esters of the 16-carbon saturated monocarboxylic acid--palmitic acid.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.
Cell surface receptors that bind somatomedins and trigger intracellular changes which influence the behavior of cells. Studies have disclosed two types of receptors for this family of peptide hormones. The type I receptor is homologous to the insulin receptor and has tyrosine kinase activity. The type II receptor is identical to the mannose-6-phosphate receptor which is important in trafficking of lysosomal enzymes.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992)
The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
The transference of pancreatic islets within an individual, between individuals of the same species, or between individuals of different species.
Self evaluation of whole blood glucose levels outside the clinical laboratory. A digital or battery-operated reflectance meter may be used. It has wide application in controlling unstable insulin-dependent diabetes.
Total number of calories taken in daily whether ingested or by parenteral routes.
A 28-amino acid, acylated, orexigenic peptide that is a ligand for GROWTH HORMONE SECRETAGOGUE RECEPTORS. Ghrelin is widely expressed but primarily in the stomach in the adults. Ghrelin acts centrally to stimulate growth hormone secretion and food intake, and peripherally to regulate energy homeostasis. Its large precursor protein, known as appetite-regulating hormone or motilin-related peptide, contains ghrelin and obestatin.
Increase in BODY WEIGHT over existing weight.
A ubiquitously expressed glucose transporter that is important for constitutive, basal GLUCOSE transport. It is predominately expressed in ENDOTHELIAL CELLS and ERYTHROCYTES at the BLOOD-BRAIN BARRIER and is responsible for GLUCOSE entry into the BRAIN.
A benign tumor of the pancreatic ISLET CELLS. Usually it involves the INSULIN-producing PANCREATIC BETA CELLS, as in INSULINOMA, resulting in HYPERINSULINISM.
An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.
A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).
A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR ALPHA is important in regulation of GLUCOSE metabolism and CELL GROWTH PROCESSES. It is a target of THIAZOLIDINEDIONES for control of DIABETES MELLITUS.
A common saturated fatty acid found in fats and waxes including olive oil, palm oil, and body lipids.
An anti-inflammatory 9-fluoro-glucocorticoid.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Severe HYPOGLYCEMIA induced by a large dose of exogenous INSULIN resulting in a COMA or profound state of unconsciousness from which the individual cannot be aroused.
Devices for simulating the activity of the pancreas. They can be either electromechanical, consisting of a glucose sensor, computer, and insulin pump or bioartificial, consisting of isolated islets of Langerhans in an artificial membrane.
Diabetes mellitus induced by PREGNANCY but resolved at the end of pregnancy. It does not include previously diagnosed diabetics who become pregnant (PREGNANCY IN DIABETICS). Gestational diabetes usually develops in late pregnancy when insulin antagonistic hormones peaks leading to INSULIN RESISTANCE; GLUCOSE INTOLERANCE; and HYPERGLYCEMIA.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
A well-characterized neutral peptide believed to be secreted by the LIVER and to circulate in the BLOOD. It has growth-regulating, insulin-like and mitogenic activities. The growth factor has a major, but not absolute, dependence on SOMATOTROPIN. It is believed to be a major fetal growth factor in contrast to INSULIN-LIKE GROWTH FACTOR I, which is a major growth factor in adults.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation.
A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.
Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).
Salts or esters of LACTIC ACID containing the general formula CH3CHOHCOOR.
An enzyme that catalyzes the conversion of D-glucose 6-phosphate and water to D-glucose and orthophosphate. EC
An essential amino acid that is physiologically active in the L-form.
The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.
Cell surface receptors that bind glucagon with high affinity and trigger intracellular changes which influence the behavior of cells. Activation of glucagon receptors causes a variety of effects; the best understood is the initiation of a complex enzymatic cascade in the liver which ultimately increases the availability of glucose to body organs.
Decrease in existing BODY WEIGHT.
BUTYRIC ACID substituted in the beta or 3 position. It is one of the ketone bodies produced in the liver.
Treatment process involving the injection of fluid into an organ or tissue.
The amount of a substance secreted by cells or by a specific organ or organism over a given period of time; usually applies to those substances which are formed by glandular tissues and are released by them into biological fluids, e.g., secretory rate of corticosteroids by the adrenal cortex, secretory rate of gastric acid by the gastric mucosa.
A normal intermediate in the fermentation (oxidation, metabolism) of sugar. The concentrated form is used internally to prevent gastrointestinal fermentation. (From Stedman, 26th ed)
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
Fatty tissue composed of WHITE ADIPOCYTES and generally found directly under the skin (SUBCUTANEOUS FAT) and around the internal organs (ABDOMINAL FAT). It has less vascularization and less coloration than the BROWN FAT. White fat provides heat insulation, mechanical cushion, and source of energy.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
A metabolic process that converts GLUCOSE into two molecules of PYRUVIC ACID through a series of enzymatic reactions. Energy generated by this process is conserved in two molecules of ATP. Glycolysis is the universal catabolic pathway for glucose, free glucose, or glucose derived from complex CARBOHYDRATES, such as GLYCOGEN and STARCH.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
Proteins prepared by recombinant DNA technology.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.

Candidate gene association study in type 2 diabetes indicates a role for genes involved in beta-cell function as well as insulin action. (1/3468)

Type 2 diabetes is an increasingly common, serious metabolic disorder with a substantial inherited component. It is characterised by defects in both insulin secretion and action. Progress in identification of specific genetic variants predisposing to the disease has been limited. To complement ongoing positional cloning efforts, we have undertaken a large-scale candidate gene association study. We examined 152 SNPs in 71 candidate genes for association with diabetes status and related phenotypes in 2,134 Caucasians in a case-control study and an independent quantitative trait (QT) cohort in the United Kingdom. Polymorphisms in five of 15 genes (33%) encoding molecules known to primarily influence pancreatic beta-cell function-ABCC8 (sulphonylurea receptor), KCNJ11 (KIR6.2), SLC2A2 (GLUT2), HNF4A (HNF4alpha), and INS (insulin)-significantly altered disease risk, and in three genes, the risk allele, haplotype, or both had a biologically consistent effect on a relevant physiological trait in the QT study. We examined 35 genes predicted to have their major influence on insulin action, and three (9%)-INSR, PIK3R1, and SOS1-showed significant associations with diabetes. These results confirm the genetic complexity of Type 2 diabetes and provide evidence that common variants in genes influencing pancreatic beta-cell function may make a significant contribution to the inherited component of this disease. This study additionally demonstrates that the systematic examination of panels of biological candidate genes in large, well-characterised populations can be an effective complement to positional cloning approaches. The absence of large single-gene effects and the detection of multiple small effects accentuate the need for the study of larger populations in order to reliably identify the size of effect we now expect for complex diseases.  (+info)

GAD2 on chromosome 10p12 is a candidate gene for human obesity. (2/3468)

The gene GAD2 encoding the glutamic acid decarboxylase enzyme (GAD65) is a positional candidate gene for obesity on Chromosome 10p11-12, a susceptibility locus for morbid obesity in four independent ethnic populations. GAD65 catalyzes the formation of gamma-aminobutyric acid (GABA), which interacts with neuropeptide Y in the paraventricular nucleus to contribute to stimulate food intake. A case-control study (575 morbidly obese and 646 control subjects) analyzing GAD2 variants identified both a protective haplotype, including the most frequent alleles of single nucleotide polymorphisms (SNPs) +61450 C>A and +83897 T>A (OR = 0.81, 95% CI [0.681-0.972], p = 0.0049) and an at-risk SNP (-243 A>G) for morbid obesity (OR = 1.3, 95% CI [1.053-1.585], p = 0.014). Furthermore, familial-based analyses confirmed the association with the obesity of SNP +61450 C>A and +83897 T>A haplotype (chi(2) = 7.637, p = 0.02). In the murine insulinoma cell line betaTC3, the G at-risk allele of SNP -243 A>G increased six times GAD2 promoter activity (p < 0.0001) and induced a 6-fold higher affinity for nuclear extracts. The -243 A>G SNP was associated with higher hunger scores (p = 0.007) and disinhibition scores (p = 0.028), as assessed by the Stunkard Three-Factor Eating Questionnaire. As GAD2 is highly expressed in pancreatic beta cells, we analyzed GAD65 antibody level as a marker of beta-cell activity and of insulin secretion. In the control group, -243 A>G, +61450 C>A, and +83897 T>A SNPs were associated with lower GAD65 autoantibody levels (p values of 0.003, 0.047, and 0.006, respectively). SNP +83897 T>A was associated with lower fasting insulin and insulin secretion, as assessed by the HOMA-B% homeostasis model of beta-cell function (p = 0.009 and 0.01, respectively). These data support the hypothesis of the orexigenic effect of GABA in humans and of a contribution of genes involved in GABA metabolism in the modulation of food intake and in the development of morbid obesity.  (+info)

How important are adult stem cells for tissue maintenance? (3/3468)

Most tissues undergo significant expansion during postnatal life, as well as a lifelong cellular turnover to compensate for cell loss. What is the identity of cells that give rise to newly differentiated cells? This fundamental yet understudied question is now attracting the attention of biologists and clinicians, triggered by reports that essentially every tissue can be replenished and repaired by multipotent adult stem cells. The identification of the "cell of origin" for a given tissue is essential for understanding its dynamics during adult life, and may have important therapeutic implications for both degenerative and neoplastic diseases. In this commentary, we briefly outline classic and current views on the question of the cell of origin. We also describe a general method that we have recently developed for addressing this issue, and its first application for the study of pancreatic beta cells.  (+info)

Advances in diabetes for the millennium: understanding insulin resistance. (4/3468)

Type 2 diabetes is a heterogeneous disorder in which both insulin resistance and impaired insulin secretion play important roles. Studies in monozygotic twins in which one is discordant for type 2 diabetes and studies of first-degree relatives of patients with type 2 diabetes who still have normal glucose tolerance indicate that impaired insulin secretion can be detected before insulin resistance, suggesting that impaired beta-cell function may be the primary genetic defect. The insulin resistance found in most individuals with impaired glucose tolerance and/or type 2 diabetes appears to be largely acquired and can be accounted for by obesity, physical inactivity, and glucose and lipotoxicity. Progressive deterioration in beta-cell function as demonstrated in the United Kingdom Prospective Diabetes Study (UKPDS) and/or worsening of insulin resistance leads to deterioration in glucose tolerance and to secondary failure of oral antidiabetic drugs. Therefore, agents that improve beta-cell function (such as sulfonylureas and meglitinides) and insulin sensitizers (such as metformin and thiazolidinediones) both are useful alone or in combination for treating type 2 diabetes.  (+info)

Dynamic interaction between T cell-mediated beta-cell damage and beta-cell repair in the run up to autoimmune diabetes of the NOD mouse. (5/3468)

In type 1 diabetes mellitus (T1DM), also known as autoimmune diabetes, the pathogenic destruction of the insulin-producing pancreatic beta-cells is under the control of and influenced by distinct subsets of T lymphocytes. To identify the critical genes expressed by autoimmune T cells, antigen presenting cells, and pancreatic beta-cells during the evolution of T1DM in the nonobese diabetic (NOD) mouse, and the genetically-altered NOD mouse (BDC/N), we used functional genomics. Microarray analysis revealed increased transcripts of genes encoding inflammatory cytokines, particularly interleukin (IL)-17, and islet cell regenerating genes, Reg3alpha, Reg3beta, and Reg3gamma. Our data indicate that progression to insulitis was connected to marked changes in islet antigen expression, beta-cell differentiation, and T cell activation and signaling, all associated with tumor necrosis factor-alpha and IL-6 expression. Overt diabetes saw a clear shift in cytokine, chemokine, and T cell differentiation factor expression, consistent with a focused Th1 response, as well as a significant upregulation in genes associated with cellular adhesion, homing, and apoptosis. Importantly, the temporal pattern of expression of key verified genes suggested that T1DM develops in a relapsing/remitting as opposed to a continuous fashion, with insulitis linked to hypoxia-regulated gene control and diabetes with C/EBP and Nkx2 gene control.  (+info)

Monogenic syndromes of abnormal glucose homeostasis: clinical review and relevance to the understanding of the pathology of insulin resistance and beta cell failure. (6/3468)

Type 2 diabetes mellitus is caused by a combination of insulin resistance and beta cell failure. The polygenic nature of type 2 diabetes has made it difficult to study. Although many candidate genes for this condition have been suggested, in most cases association studies have been equivocal. Monogenic forms of diabetes have now been studied extensively, and the genetic basis of many of these syndromes has been elucidated, leading to greater understanding of the functions of the genes involved. Common variations in the genes causing monogenic disorders have been associated with susceptibility to type 2 diabetes in several populations and explain some of the linkage seen in genome-wide scans. Monogenic disorders are also helpful in understanding both normal and disordered glucose and insulin metabolism. Three main areas of defect contribute to diabetes: defects in insulin signalling leading to insulin resistance; defects of insulin secretion leading to hypoinsulinaemia; and apoptosis leading to decreased beta cell mass. These three pathological pathways are reviewed, focusing on rare genetic syndromes which have diabetes as a prominent feature. Apoptosis seems to be a final common pathway in both type 1 and type 2 diabetes. Study of rare forms of diabetes may help ion determining new therapeutic targets to preserve or increase beta cell mass and function.  (+info)

Human bone marrow mesenchymal stem cells can express insulin and key transcription factors of the endocrine pancreas developmental pathway upon genetic and/or microenvironmental manipulation in vitro. (7/3468)

Multipotential stem cells can be selected from the bone marrow by plastic adhesion, expanded, and cultured. They are able to differentiate not only into multiple cell types, including cartilage, bone, adipose and fibrous tissues, and myelosupportive stroma, but also into mesodermal (endothelium), neuroectodermal, or endodermal (hepatocytes) lineages. Our goal was to characterize the multipotential capacities of human mesenchymal stem cells (hMSCs) and to evaluate their ability to differentiate into insulin-secreting cells in vitro. hMSCs were obtained from healthy donors, selected by plastic adhesion, and phenotyped by fluorescence-activated cell sorter and reverse transcription-polymerase chain reaction analysis before and after infection with adenoviruses coding for mouse IPF1, HLXB9, and FOXA2 transcription factors involved early in the endocrine developmental pathway. We found that native hMSCs have a pluripotent phenotype (OCT4 expression and high telomere length) and constitutively express NKX6-1 at a low level but lack all other transcription factors implicated in beta-cell differentiation. In all hMSCs, we detected mRNA of cytokeratin 18 and 19, epithelial markers present in pancreatic ductal cells, whereas proconvertase 1/3 mRNA expression was detected only in some hMSCs. Ectopic expression of IPF1, HLXB9, and FOXA2 with or without islet coculture or islet-conditioned medium results in insulin gene expression. In conclusion, our results demonstrated that in vitro human bone marrow stem cells are able to differentiate into insulin-expressing cells by a mechanism involving several transcription factors of the beta-cell developmental pathway when cultured in an appropriate microenvironment.  (+info)

ELKS, a protein structurally related to the active zone-associated protein CAST, is expressed in pancreatic beta cells and functions in insulin exocytosis: interaction of ELKS with exocytotic machinery analyzed by total internal reflection fluorescence microscopy. (8/3468)

The cytomatrix at the active zone (CAZ) has been implicated in defining the site of Ca2+-dependent exocytosis of neurotransmitters. Here, we demonstrate the expression and function of ELKS, a protein structurally related to the CAZ protein CAST, in insulin exocytosis. The results of confocal and immunoelectron microscopic analysis showed that ELKS is present in pancreatic beta cells and is localized close to insulin granules docked on the plasma membrane-facing blood vessels. Total internal reflection fluorescence microscopy imaging in insulin-producing clonal cells revealed that the ELKS clusters are less dense and unevenly distributed than syntaxin 1 clusters, which are enriched in the plasma membrane. Most of the ELKS clusters were on the docking sites of insulin granules that were colocalized with syntaxin 1 clusters. Total internal reflection fluorescence images of single-granule motion showed that the fusion events of insulin granules mostly occurred on the ELKS cluster, where repeated fusion was sometimes observed. When the Bassoon-binding region of ELKS was introduced into the cells, the docking and fusion of insulin granules were markedly reduced. Moreover, attenuation of ELKS expression by small interfering RNA reduced the glucose-evoked insulin release. These data suggest that the CAZ-related protein ELKS functions in insulin exocytosis from pancreatic beta cells.  (+info)

In islets from individuals with type 2 diabetes and in islets exposed to chronic elevated glucose, mitochondrial energy metabolism is impaired. Here, we studied early metabolic changes and mitochondrial adaptations in human beta cells during chronic glucose stress.Respiration and cytosolic ATP changes were measured in human islet cell clusters after culture for 4 days in 11.1 mmol/l glucose. Metabolomics was applied to analyse intracellular metabolite changes as a result of glucose stress conditions. Alterations in beta cell function were followed using insulin secretion assays or cytosolic calcium signalling after expression of the calcium probe YC3.6 specifically in beta cells of islet clusters.At early stages of glucose stress, mitochondrial energy metabolism was augmented in contrast to the previously described mitochondrial dysfunction in beta cells from islets of diabetic donors. Following chronic glucose stress, mitochondrial respiration increased (by 52.4%, p ...
Type 2 diabetes can be viewed as a failure of the pancreatic beta-cell to compensate for peripheral insulin resistance with enhanced insulin secretion. This failure is explained by both a relative loss of beta-cell mass as well as secretory defects that include enhanced basal secretion and a selective loss of sensitivity to glucose. These features are reproduced by chronic exposure of beta-cells to fatty acids (FAs), suggesting that hyperlipidemia might contribute to decompensation. Using MIN6 cells pretreated for 48 h with oleate or palmitate, we have previously defined alterations in global gene expression by transcript profiling and described additional secretory changes to those already established (Busch A-K, Cordery D, Denyer G, Biden TJ: Diabetes 51:977-987, 2002). In contrast to a modest decoupling of glucose-stimulated insulin secretion, FA pretreatment markedly enhanced the secretory response to an acute subsequent challenge with FAs. We propose that this apparent switch in sensitivity from
Understanding the molecular mechanisms behind beta cell dysfunction is essential for the development of effective and specific approaches for diabetes care and prevention. Physiological human beta cell models are needed for this work. We review the possibilities and limitations of currently availabl …
Developmental insults during gestation, such as under-nutrition, are known to restrict the number of beta cells that form in the fetal pancreas and are maintained in adulthood, leading to increased risk of type 2 diabetes. There are now substantial data indicating that glucocorticoids mediate this effect of under-nutrition on beta cell mass and that even at physiological levels they restrain fetal beta cell development in utero. There are emerging clues that this occurs downstream of endocrine commitment by neurogenin 3 but prior to terminal beta cell differentiation. Deciphering the precise mechanism will be important as it might unveil new pathways by which to manipulate beta cell mass that could be exploited as novel therapies for patients with diabetes.. ...
Analysis of Beta-Cell Gene Expression Reveals Inflammatory Signaling and Evidence of Dedifferentiation following Human Islet Isolation and Culture. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
GSIS assays (Glucose Stimulated Insulin Secretion) have been the gold-standard for determining the functionality of a beta cell. Study of dynamic insulin release with perfusion assays is a crucial component of beta cell research. Up to now, heterogeneity in islet size and composition decreased experimental resolution, limits reproducibility and capability of using human islets for medium or large throughput GSIS screening and assay modeling. Both scientists from academia and industry are looking for large quantity of robust and functional human beta cells.. There is a growing need for better predictive tools to assess human beta cell dysfunction early in the drug development process. The authors at Novo Nordisk note in their publication, that they have now successfully used EndoC-βH1 as a screening platform for early drug discovery with regards to insulin secretion and beta cell proliferation and identified several interesting peptides and proteins. According to the authors from Novo ...
Researchers at the Icahn School of Medicine at Mount Sinai have discovered a novel combination of two classes of drugs that, together, cause the highest rate of proliferation ever observed in adult human beta cells-the cells in the pancreas that produce insulin-without harming most other cells in the body. The result is an important step toward a diabetes treatment that restores the bodys ability to produce insulin.. The finding involved one type of drug that is known to cause beta cells to proliferate and another that is already in widespread use in people with diabetes. Together, they caused the cells to proliferate at a rate of 5 to 6 percent per day. The study was published today in Science Translational Medicine online.. We are very excited about this new drug combination because for the first time ever, we are able to see rates of human beta-cell replication that are sufficient to replenish beta-cell mass in humans with diabetes, said Andrew Stewart, MD, Director of the Mount Sinai ...
Shop Pancreatic beta cell growth factor ELISA Kit, Recombinant Protein and Pancreatic beta cell growth factor Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
Glucagon-like peptide-1 (GLP-1), an insulinotropic and glucoincretin hormone, is a potentially important therapeutic agent in the treatment of diabetes. We previously provided evidence that GLP-1 induces pancreatic beta-cell growth nonadditively with glucose in a phosphatidylinositol-3 kinase (PI-3K)-dependent manner. In the present study, we investigated the downstream effectors of PI-3K to determine the precise signal transduction pathways that mediate the action of GLP-1 on beta-cell proliferation. GLP-1 increased extracellular signal-related kinase 1/2, p38 mitogen-activated protein kinase (MAPK), and protein kinase B activities nonadditively with glucose in pancreatic beta(INS 832/13) cells. GLP-1 also caused nuclear translocation of the atypical protein kinase C (aPKC) zeta isoform in INS as well as in dissociated normal rat beta-cells as shown by immunolocalization and Western immunoblotting analysis. Tritiated thymidine incorporation measurements showed that the p38 MAPK inhibitor SB203580
The prevalence of Diabetes Mellitus has reached epidemic proportions world-wide, and is predicted to increase rapidly in the years to come, putting a tremendous strain on health care budgets in both developed and developing countries. There are two major forms of diabetes and both are associated with decreased beta-cell mass. No treatments have been devised that increase beta-cell mass in vivo in humans, and transplantation of beta-cells is extremely limited due to lack of appropriate donors. For these reasons, increasing functional beta-cell mass in vitro, or in vivo prior to or after transplantation, has become a Holy Grail of diabetes research. Our previous studies clearly show that adult human beta-cells can be induced to replicate, and - importantly - that cells can maintain normal glucose responsiveness after cell division. However, the replication rate achieved was still low, likely due in part to the known age-related decline in the ability of the beta-cell to replicate. We propose to ...
Insulin resistance and pancreatic beta cell dysfunction are major contributors to the pathogenesis of diabetes. Various conditions play a role in the pathogenesis of pancreatic beta cell dysfunction and are correlated with endoplasmic reticulum (ER) stress. Pancreatic beta cells are susceptible to ER stress. Many studies have shown that increased ER stress induces pancreatic beta cell dysfunction and diabetes mellitus using genetic models of ER stress and by various stimuli. There are many reports indicating that ER stress plays an important role in the impairment of insulin biosynthesis, suggesting that reduction of ER stress could be a therapeutic target for diabetes. In this paper, we reviewed the relationship between ER stress and diabetes and how ER stress controls insulin biosynthesis.
Recent studies suggested that in older mice, beta cells lose their regenerative potential and cannot respond to mitogenic triggers. in replication rate of beta cells 64048-12-0 in young transgenic mice. Islet architecture and glucose threshold slowly normalized, indicating practical significance of compensatory beta cell replication in this establishing. Finally, administration of a small molecule glucokinase activator to older mice doubled the rate of recurrence of beta cell replication, further showing that older 64048-12-0 beta cells can respond to the mitogenic result in of enhanced glycolysis. We consider that the potential for functionally significant compensatory expansion of beta cells is definitely retained in older mice, despite a decrease in basal replication rate. test. A value < 0.05 was considered significant. Data are offered as mean H.E. RESULTS Beta Cell Mutilation in Old Mice To characterize the characteristics of beta cell mutilation in older mice, we prepared a cohort of ...
phdthesis{ef479246-001e-4db0-bb31-b145ccaa5214, abstract = {Beta cell function is an important factor in the development of both Type 1 (T1D) and Type 2 (T2D) diabetes mellitus. T1D is characterized by a primary defect in insulin secretion due to the immune-mediated beta cell destruction, however, the more common T2D beside insulin resistance also include impaired beta cell function as a consequence to abnormal glucose homeostasis. Genetic susceptibility is involved in both types of diabetes. We have studied several genetic and immunological factors affecting beta cell function. ,br/,,br, ,br/,,br, First, we tested whether single nucleotide polymorphisms (SNPs) of the human Free Fatty Acid Receptor 1 (FFAR1) are associated with T2D and insulin secretion. Another genetic study focused on FOXP3 association with T1D and the disease-related clinical parameters. The role of microRNAs (miRNAs) on beta cell function was studied in the third project using a novel genetically engineered mouse model. ...
Foodborne Cereulide Causes Beta-Cell Dysfunction and Apoptosis. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
TY - JOUR. T1 - Circulating Unmethylated Insulin DNA As a Biomarker of Human Beta Cell Death. T2 - A Multi-laboratory Assay Comparison. AU - Speake, Cate. AU - Ylescupidez, Alyssa. AU - Neiman, Daniel. AU - Shemer, Ruth. AU - Glaser, Benjamin. AU - Tersey, Sarah A.. AU - Usmani-Brown, Sahar. AU - Clark, Pamela. AU - Wilhelm, Joshua J.. AU - Bellin, Melena D.. AU - Herold, Kevan C.. AU - Mirmira, Raghavendra G.. AU - Dor, Yuval. AU - Evans-Molina, Carmella. N1 - Funding Information: Funding Statement: This research was performed using funding provided by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)-supported Human Islet Research Network Opportunity Pool Fund (HIRN, RRID:SCR_014393; https://hirnetwork.org; U01 DK104162 to CEM), and by JDRF under the Core for Assay Validation grants #3-SRA-2016-209-Q-R to S. Alice Long and 3-SRA-2019-791-S-B to CS. KCH received support from R01 DK057846, UC4 DK104205-01, and R21 AI135562. KCH and SUB have support from R43 DK116577. ...
We present evidence that, in addition to immune cell types, mouse and human pancreatic beta cells express CD40. Its expression is upregulated by proinflammatory stimuli, and signalling through this receptor activates NF-kappaB. We suggest that the effects of inflammatory stimuli that affect beta cel …
all beta cells and people with the disease would have to take insulin for life But we know that some beta cells do survive and secrete insulin even when the patients have had type 1 diabetes for 50 years says senior author Rohit N Kulkarni M D Ph D Associate Professor of Medicine at Harvard Medical School and the principle investigator of the project at Joslin In this study Joslin researchers were interested in learning exactly how immune cells could promote beta cell growth and identifying the type of cell and the mechanisms underlying this effect In a series of experiments the researchers injected NOD mice with immune cells from the pancreatic islets of donor NOD mice and assessed their effects on beta cells The immune cells tested included subtypes of B or T immune cells Dirice the lead author of the study found that it is T cells not B cells that are associated with beta cell proliferation Mice that received B cells showed no difference in beta cell growth Mice that received the T cell ...
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Increased glycemic variability has been proposed as an independent predictor of hypoglycemia in diabetic patients. Likewise, episodes of dysglycemia have been found to be predictive of diabetes in antibodypositive nondiabetic individuals. We hypothesise that an in-depth observational study comparing state-of-the-art measures of functional beta cell mass and glycemic variability will specify the relationship between both variables over a broad range of residual function and will identify treatment goals for functional beta cell mass to be reached in future beta cell therapy trials in order to avoid frequent hypoglycemia in patients and dysglycemia in risk groups. The available expertise and infrastructure (see background and (inter)national context) place the promoters of the present project in a unique position to carry out the planned experiments and support their feasibility ...
Juan-Mateu, Jonàs et al SRp55 Regulates a Splicing Network that Controls Human Pancreatic Beta Cell Function and Survival. Diabetes (2017): db170736. Web. 22 Jan. 2018. ...
While the mechanisms by which glucose regulates insulin secretion from pancreatic beta cells are now well described, the way glucose modulates gene expression in such cells needs more understanding. Here, we demonstrate that MondoA, but not its paralogue ChREBP, is the predominant glucose-responsive transcription factor in human pancreatic beta EndoC-βH1 cells and in human islets. In high glucose conditions, MondoA shuttles to the nucleus where it is required for the induction of the glucose-responsive genes ARRDC4 and TXNIP, the latter being a protein strongly linked to beta-cell dysfunction and diabetes. Importantly, increasing cAMP signaling in human beta cells, using forskolin or the GLP-1 mimetic Exendin-4, inhibits the shuttling of MondoA and potently inhibits TXNIP and ARRDC4 expression. Furthermore, we demonstrate that silencing MondoA expression improves glucose uptake in EndoC-βH1 cells. These results highlight MondoA as a novel target in beta cells that coordinates transcriptional ...
Our What?. One of the family of signals that the Huising lab studies, is named for the stress peptide Corticotropin Releasing Factor, or CRF in short. CRF was originally discovered as the principal hypothalamic factor to initiate the stress response by acting on the pituitary gland. It turns out that the insulin-producing beta cells of the pancreas can respond directly to CRF with increased insulin secretion, increased beta cell proliferation and reduced beta cell death in the face of pro-inflammatory insults, which is a promising set of beneficial characteristics united in a single molecule. Urocortin3 (Ucn3), a peptide related to CRF, is abundantly expressed by mature beta cells. We discovered that Ucn3 is co-released with insulin to trigger somatostatin release from neighboring delta cells, which in turn inhibits insulin secretion. In essence, Ucn3 triggers a negative feedback loop that attenuates insulin secretion, provided that glucose levels are successfully reduced. Ucn3 expression also ...
BACKGROUND: The expression of interleukin-1-receptor antagonist is reduced in pancreatic islets of patients with type 2 diabetes mellitus, and high glucose concentrations induce the production of interleukin-1beta in human pancreatic beta cells, leading to impaired insulin secretion, decreased cell proliferation, and apoptosis. METHODS: In this double-blind, parallel-group trial involving 70 patients with type 2 diabetes, we randomly assigned 34 patients to receive 100 mg of anakinra (a recombinant human interleukin-1-receptor antagonist) subcutaneously once daily for 13 weeks and 36 patients to receive placebo. At baseline and at 13 weeks, all patients underwent an oral glucose-tolerance test, followed by an intravenous bolus of 0.3 g of glucose per kilogram of body weight, 0.5 mg of glucagon, and 5 g of arginine. In addition, 35 patients underwent a hyperinsulinemic-euglycemic clamp study. The primary end point was a change in the level of glycated hemoglobin, and secondary end points were ...
D-glucose regulates maintenance and function of pancreatic beta-cells. Several studies have shown that IRS-2, but not IRS-1, is necessary to maintain and sufficient to expand functional beta-cell mass. We therefore analyzed the expression of IRS-2 and IRS-1 in beta-cells after culture in the presence of various concentrations of D-glucose and other metabolisable or non-metabolisable hexoses. D-glucose increased Irs-2 transcription and IRS-2 accumulation in a dose-dependent manner (1.6 to 25 mmol/l), with a 3-fold increased plateau after 10 h. In contrast, the expression of IRS-1 remained unaffected. D-glucose also induced phosphorylation of IRS-2 while non-metabolisable hexoses did neither affect expression nor phosphorylation. D-glucose-mediated elevation and phosphorylation of IRS-2 were independent of autocrine insulin action although insulin itself could transiently and slightly enhance IRS-2 expression. ...
Prof. Melton stated his optimism about the future of diabetes treatment: Semmas scientists have very effectively dedicated themselves to systems that reliably generate cells indistinguishable from human pancreatic beta cells and to the invention of novel devices that are immunologically protective and surgically practical. Were very encouraged and excited about the potential this program has for diabetic patients and their families.. ...
Several groups have overexpressed Pdx1 protein in the liver of STZ-induced diabetic mice but have not succeeded in producing selective pancreatic endocrine differentiation (4,6,7,21). Instead, severe hepatitis, presumably caused by the production of exocrine enzymes such as amylase, elastase, and chymotrypsin (7), and dysmorphogenesis, such as abnormal lobe structures and multiple cystic lesions (21), were recently reported. The conclusion drawn from these in vivo animal studies is that ectopic expression of Pdx1 alone in the liver initiates both endocrine and exocrine pancreas differentiation and is insufficient to induce selective endocrine pancreas differentiation. Recent work by Zalzman et al. (22) has shown that introduction of Pdx1 into human fetal liver progenitor cells by lentivirus resulted in the expression of Ngn3, Beta2, and Nkx6.1 genes, but not Nkx2.2, Isl-1, Pax4, and Pax6 genes and was able to rescue diabetic mice, although a complete analysis was not performed. This observation ...
With an RD Lawrence Fellowship from Diabetes UK, Dr Cantley will use state-of-the-art techniques in molecular and cell biology to study the mechanisms by which ACC1 works in human and mouse beta cells in the laboratory. Specifically, he will look at the influence of ACC1 on beta cell size and number in response to metabolic challenges such as obesity and pregnancy. Dr Cantley will focus on ACC1 activity in mice, isolated mouse islets, mouse and human beta cells in the lab, and human islets. He will then monitor its impact on different aspects of beta cell function (such as insulin release, cell structure within the pancreas and the expression of genes and proteins).. ...
With a single stimulatory molecule, human insulin-producing beta cell replication can be sustained for at least four weeks in a mouse model of diabetes...
Oxidative Medicine and Cellular Longevity is a unique peer-reviewed, Open Access journal that publishes original research and review articles dealing with the cellular and molecular mechanisms of oxidative stress in the nervous system and related organ systems in relation to aging, immune function, vascular biology, metabolism, cellular survival and cellular longevity. Oxidative stress impacts almost all acute and chronic progressive disorders and on a cellular basis is intimately linked to aging, cardiovascular disease, cancer, immune function, metabolism and neurodegeneration. The journal fills a significant void in todays scientific literature and serves as an international forum for the scientific community worldwide to translate pioneering
A hot topic in the type 2 diabetes world is whether we have in hand the tools to stop the decline in beta cell function that typifies this disease and, consequently, a therapy or therapies that successfully control blood glucose for many years - so-called treatment durability. Actually this is three topics. What are the specific mechanisms for the beta cell failure? Do any of our existing therapies, or those on the drawing board, reverse these mechanisms to slow or stop the beta cell failure? ...
Insufficient pancreatic beta-cell mass is fundamental to the pathogenesis of both types 1 and 2 diabetes and constitutes the basis for the goal of beta-cell replacement therapy. Current methods for isolating islets from organ donor pancreases do not come close to supplying all in need, thus providing a compelling need to find new sources of insulin-producing cells. Possible sources include generation of cells from embryonic stem cells (ESC), adult stem/precursor cells, transdifferentiation of other cell types and xenodonors. Bioengineering can be used to improve secretory performance and strengthen cells to better withstand the challenges of transplantation. Strategies include protection against hypoxia, inflammation, and immune attack.
Compromised function of insulin-secreting pancreatic β cells is central to the development and progression of Type 2 Diabetes (T2D). However, the mechanisms underlying β cell failure remain incompletely understood. Here, we report that metabolic stress markedly enhances macroautophagy-independent lysosomal degradation of nascent insulin granules. In different model systems of diabetes including of human origin, stress-induced nascent granule degradation (SINGD) contributes to loss of insulin along with mammalian/mechanistic Target of Rapamycin (mTOR)-dependent suppression of macroautophagy. Expression of Protein Kinase D (PKD), a negative regulator of SINGD, is reduced in diabetic β cells. Pharmacological activation of PKD counters SINGD and delays the onset of T2D. Conversely, inhibition of PKD exacerbates SINGD, mitigates insulin secretion and accelerates diabetes. Finally, reduced levels of lysosomal tetraspanin CD63 prevent SINGD, leading to increased insulin secretion. Overall, our findings
In vitro expansion of beta-cells from adult human islets could solve the tissue shortage for cell replacement therapy of diabetes. Culture of human islet cells typically results in |16 cell doublings and loss of insulin expression. Using cell lineage
Viral infections and local production of IFNgamma might contribute to beta-cell dysfunction/death in Type 1 diabetes. Double stranded RNA accumulates in the cytosol of viral-infected cells, and exposure of purified rat beta cells to dsRNA (polyinosinic-polycytidylic acid, PIC) in combination with IFNgamma results in beta-cell dysfunction and apoptosis. To elucidate the molecular mechanisms involved in PIC + IFNgamma-effects, we determined the global profile of genes modified by these agents in primary rat beta cells. FACS-purified rat beta cells were cultured for 6 or 24 h in control condition or with IFNgamma, PIC or a combination of both agents. The gene expression profile was analyzed in duplicate with the Affymetrix RG U34A microarray.
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As reported by JDRF, funded scientists at the University of Pittsburgh in America have uncovered a new way to grow human beta cells in the lab.. The team led by Professor Andrew Stewart, were able to get human beta cells to divide and make more cells. Not only that, but they then managed to stop the cells dividing again. The research was published in this months issue of the journal Diabetes.. The researchers added genes called cdk and cyclin d into the beta cells. These genes make the cells divide and are usually switched off in beta cells. To deliver these genes into the cells they used a virus that can get into cells easily. Once they had enough beta cells, they added a drug to the cells which switched off the virus and stopped the cells dividing.. In the body, beta cells divide very slowly or not at all so when the immune system attacks them, the cells are not replaced. Usually in type 1 diabetes there are a few beta cells remaining and if scientists could make these cells divide they could ...
Type 2 diabetes mellitus (T2DM) is a complex metabolic disease characterized by the loss of beta-cell secretory function and mass. The pathophysiology of beta-cell failure in T2DM involves a complex...
Human beta cell proliferation was once unthinkable, but now it is absolutely possible, says the senior author of a new study in cell cultures and in mice. The field is moving rapidly.
Its important to remember that individual cells do not last as long as people live. Cells naturally die and new cells grow within your body all the time. Research (mostly in animals) has suggested that Vildagliptin might have two separate effects on beta cells. On the one hand, it seems to cause beta cells to naturally divide and grow, and on the other hand, it seems to delay beta cells natural death, so they live longer. Both of these effects may be important to curing type-1 diabetes, but it is not clear. This is why research is important. For example, even if Vildagliptin triggers a divide-and-grow reaction, it will only be effective if there are some beta cells to start with, and we just dont know if there are enough to get things started. On the cell death side, if the autoimmune attack directly kills beta cells, then stopping natural cell death may have little impact. Those cells will be killed by autoimmunity before they can die of old age. However, if the autoimmune attack works ...
Their non-profit company, Tenth Muse Films, hopes to raise the curtain in 2017 on The Human Trial, a film that will showcase the need for sustained philanthropic investment to bring about breakthrough technologies, in this case the implantation of pancreatic cells. Their first project is focused on ViaCyte, a San Diego biotech which is trying to use a novel approach to implant pancreatic progenitor cells into people with diabetes that will mature into functional beta cells. (The filmmakers have no affiliation nor financial connection with any of the companies or entities appearing in the film.). ViaCyte is testing a product identified as a VC-01 combination device. Its a mesh pouch encapsulated in a pliable membrane which allows hormones, metabolic fluids, and oxygen to migrate, but resists immune system T-cell invasion. T-cells in people with Type 1 often target implanted beta cells, making beta cell transplant a very frustrating treatment option.. The VC-01, dubbed the teabag, is designed ...
Researchers in the lab of Gordon Weir, M.D., looked at a cellular stress mechanism called the unfolded protein response or endoplasmic reticulum (ER) stress response in beta cells. This response is triggered when the ER, part of the cells protein assembly line, struggles to fold newly formed proteins into their exactly right shapes.. Earlier studies suggested this process contributes to the high mortality and low insulin production often displayed in beta cell transplants, which aim to replace cells that the bodys own immune system kills off in type 1 diabetes.. In work reported in the journal PLoS One in June, the scientists compared healthy human beta cells from surgical donors with beta cells that had been transplanted into mice with suppressed immune systems. They found that the transplanted cells strongly activate genes that help to guard against damage from ER stress, and suppress other genes that may trigger cellular attempts to self-destruct.. Not only is this response likely to be ...
J:194010 Iglesias J, Barg S, Vallois D, Lahiri S, Roger C, Yessoufou A, Pradevand S, McDonald A, Bonal C, Reimann F, Gribble F, Debril MB, Metzger D, Chambon P, Herrera P, Rutter GA, Prentki M, Thorens B, Wahli W, PPARbeta/delta affects pancreatic beta cell mass and insulin secretion in mice. J Clin Invest. 2012 Nov 1;122(11):4105-17 ...
Search PubMed for more publications by Feyza Engin. 1. Engin, F. ER Stress and Development of Type 1 Diabetes J Investig Med. 2015.. 2. Brozzi, F., Nardelli, TR., Lopes, M., Millard, I., Barthson, J., Igoillo-Esteve, M., Grieco, FA., Villate, O., Oliveira, JM., Casimir, M., Bugliani, M., Engin, F., Hotamisligil, GS., Marchetti, PM., Eizirik, DL. Cytokines induce endoplasmic reticulum stress in human, rat and mouse beta cells via different mechanisms. Diabetologia. 2015.. 3. Engin, F., Ngyuen T., Yermalovich A., Hotamisligil, GS. Aberrant unfolded protein response in type 2 diabetes. Sci Rep. 2014.. 4. Engin, F., Yermalovich, A., Fu, W., Ngyuen, T., Hummasti, S., Decio, L., Eizirik., Mathis, D., Hotamisligil, GS. Restoration of the unfolded protein response in pancreatic beta cells protects mice against type 1 diabetes. Sci. Transl. Med. 2013.. 5. Engin, F., Hotamisligil, GS. Chemical modulation of ER function in metabolic diseases. Diabetes Obes. Metab. 2010. 12 Suppl 2:108-15.. 6. ...
Over the past several years, JDRF-funded researchers have found evidence that beta cell stress may play a role in the onset of T1D, and are exploring possible ways to stop it from occurring, thus potentially protecting beta cell health and maintaining normal beta cell function. In April, JDRF-funded researchers in Finland released new findings in the journal CellPress that add another piece to the puzzle of beta cell stress and T1D.
But what if other cells in the body could be coaxed into ever pancreatic beta cells? Could we possibly cure diabetes?Researchers at UCLA Larry L www.erectalis
Pretreatment of pancreatic beta cells with pertussis toxin resulted in a 30% increase in peak whole-cell Ca2+ currents recorded in the absence of exogenous intracellular guanine nucleotides. Intracellular application of 90 microM GTP[gamma S], by liberation from a caged precursor, resulted in 40% reduction of the peak Ca2+ current irrespective of whether the current was carried by Ca2+ or Ba2+. Effects on the delayed outward K+ current were small and restricted to a transient Ca(2+)-dependent K+ current component. Inhibition by GTP[gamma S] of the Ca2+ current was not mimicked by standard GTP and could not be prevented either by pretreatment with pertussis toxin or by inclusion of GDP[beta S] or cyclic AMP in the intracellular medium. The inhibitory effect of GTP[gamma S] could be counteracted by a prepulse to a large depolarizing voltage. A similar effect of a depolarizing prepulse was observed in control cells with no exogenous guanine nucleotides. These observations indicate that inhibition of beta
Author: Gylfe, E. et al.; Genre: Journal Article; Published in Print: 1993-08; Title: Triphasic changes of cytoplasmic CA2+ associated with early glucose effects on beta-cell membrane potential.
In This Section1 What is Type 2 Diabetes?2 Pre-diabetes3 Genetics and Beta Cell Function4 Beta Cell Function Decline and Progression to Diabetes5 Obesity and Beta Cell Function6 Beta Cell Failure7 Summary8 References What is Type 2 Diabetes? Type 2 diabetes is characterized by abnormally high blood glucose levels. The disease is multifactorial and has several risk factors, including obesity and family history. Type 2 diabetes occurs when the pancreatic beta cells that secrete insulin become dysfunctional. At first, the beta cells release large amounts of insulin to compensate for the elevated blood glucose levels. Over time the disease can progress to the point of complete beta cell failure and patients can become dependent on insulin replacement therapy. Pre-diabetes Pre-diabetes is characterized by blood glucose levels that are elevated but not high enough for a diabetes diagnosis. Typically, a hemoglobin A1c level of 5.7% - 6.4% is indicative of pre-diabetes. Patients
TY - JOUR. T1 - Hydrochlorothiazide: An hyperglycaemia-inducing agent and K-ATP channel agonist in human beta-cells and clonal insulin-secreting cells.. AU - Barnes, PD. AU - OBrien, RE. AU - Abdel-Wahab, Yasser. AU - Cosgrove, KE. AU - Flatt, Peter. AU - Dunne, MJ. PY - 1999/8. Y1 - 1999/8. M3 - Article. VL - 42. SP - 482. JO - Diabetologia. JF - Diabetologia. SN - 0012-186X. IS - Suppl.. ER - ...
Wolfram syndrome, also referred to as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) is a genetic syndrome characterized by beta-cell dysfunction and apoptosis leading to diabetes, neurodegeneration and psychiatric illness. Accumulating evidence indicates that beta-cell failure and neuronal cell dysfunction in Wolframs syndrome results from a high level of ER stress in affected cells. The current treatment of Wolfram syndrome is insulin, which fails to prevent the progression of beta-cell failure.. Several studies showed that GLP-1 analogs are very effective in protecting beta-cells from ER stress. Herein, the investigators suggest studying the impact of GLP-1 analogs in the treatment of patients with Wolfram syndrome.. The investigators will Study the effects of GLP-1 analog (Exanatide) on beta-cell function and glycemic control of patients with Wolfram syndrome. Evaluation of beta cell function will be done by performing meal test and IVGTT test before starting ...
The various endocrine cell types present in mammalian Islets of Langerhans express a range of lipid-responsive G-proteln coupled receptors (GPCRs) including GPR119 and GPR120. These are each reported to be expressed In islet beta-cells and GPR 119 has been Implicated In the augmentation of glucose-stimulated insulin secretion by certain derivatives of long chain unsaturated fatty acids. By contrast GPR 120 does not appear to regulate insulin secretion and its role is unclear In addition to their ability to regulate hormone secretion long-chain fatty acids and their derivatives can also influence beta-cell viability but It IS unclear whether GPCRs are involved in mediating this response Therefore. the work undertaken in thesis has explored the possible involvement of GPR119 and GPR120 in the regulation of beta-cell viability. Long chain fatty acids exert differential effects on beta-cell viabilty according to their chain length and degree of unsaturation. Saturated molecules with chain lengths of ...
This study will compare the effects of olmesartan medoxomil and amlodipine on beta-cell function and the incidence diabetic angiopathy in type 2 diabetic
The beta cells are particularly important because they make insulin. Degeneration of the beta cells is the main cause of type I (insulin-dependent) diabetes mellitus.
Previously published gene expression analyses suggested that apoptotic function may be reduced in humans relative to chimpanzees and led to the hypothesis that this difference may contribute to the relatively larger size of the human brain and the increased propensity of humans to develop cancer. In this study, we sought to further test the hypothesis that humans maintain a reduced apoptotic function relative to chimpanzees by conducting a series of apoptotic function assays on human, chimpanzee and macaque primary fibroblastic cells. Human cells consistently displayed significantly reduced apoptotic function relative to the chimpanzee and macaque cells. These results are consistent with earlier findings indicating that apoptotic function is reduced in humans relative to chimpanzees.
Brusatol is a natural terpenoid that is capable of inducing a variety of biological effects. We presently report that this substance dramatically improves beta-cell survival when exposed to pro-inflammatory cytokines (IL-1 beta and IFN gamma) in vitro. This was observed in insulin producing rat (RIN-5AH), mouse (beta TC6) and human (EndoC-beta H1) beta-cell lines. Brusatol prevented beta-cell oxidative stress in response to cytokines and counteracted induction of iNOS on the protein level. Brusatol, however, block neither the cytokine-induced increase of iNOS mRNA, nor NF-kappa B activation, suggesting that inhibition of iNOS protein expression relies on posttranscriptional mechanism. This indicates that brusatol acts via a novel protective pathway, which may represent a more promising way of improving beta-cell function and survival.. ...
AIM/HYPOTHESIS: Increased expression of haeme-oxygenase 1 (HO1) and other antioxidant enzymes could improve pancreatic beta-cell survival under stressful conditions, including hyperglycaemia. However, how hyperglycaemia increases islet HO1 expression is not known. METHODS: Rat islets were pre-cultured for 1 week in RPMI medium containing 10 mmol x l(-1) glucose (G10), and further cultured overnight in G5-G30 plus various test substances. Islet HO1 mRNA and protein expression was measured by semiquantitative RT-PCR, western blot, and immunohistochemistry. RESULTS: Islet HO1 mRNA expression was minimal after overnight culture in G10, slightly increased in G5, and increased by five- to ten-fold in G30 in parallel with a heterogeneous increase in beta-cell HO1 protein expression. The effect of G30 was fully inhibited by agents decreasing cytosolic Ca2+ (diazoxide, nimodipine), but was only slightly reproduced by agents raising Ca2+ (tolbutamide, 30 mmol x l(-1) potassium). It was also suppressed by ...
IGFs are important regulators of pancreatic beta-cell development, growth, and maintenance. Mutations in the IGF genes have been found to be associated with type 2 diabetes, myocardial infarction, birth weight, and obesity. These associations could result from changes in insulin secretion. We have analyzed glucose-stimulated insulin secretion using hyperglycemic clamps in carriers of a CA repeat in the IGF-I promoter and an ApaI polymorphism in the IGF-II gene. Normal and impaired glucose-tolerant subjects (n = 237) were independently recruited from three different populations in the Netherlands and Germany to allow independent replication of associations. Both first- and second-phase insulin secretion were not significantly different between the various IGF-I or IGF-II genotypes. Remarkably, noncarriers of the IGF-I CA repeat allele had both a reduced insulin sensitivity index (ISI) and disposition index (DI), suggesting an altered balance between insulin secretion and insulin action. Other diabetes
Preparation of Recombinant Adenoviruses. All first-generation recombinant adenoviruses were constructed according to Becker et al. (18). Generation of Ad-RIP-GFP and the bifunctional recombinant Ad-RIP-GFP-CMV-PDX-1 adenoviruses is described in Supporting Methods, which is published as supporting information on the PNAS web site.. Human Liver Cells. Adult human liver (AHL) tissues were obtained from eight different liver transplantation surgeries from 4- to 10-year-old children and three individuals ,40 years old. Fetal human livers were obtained from four deliberate abortions of 20-22 weeks of gestation. Both adult and fetal liver tissues were used with approval from the Committee on Clinical Investigations (Institutional Review Boards of Sheba Medical Center and Rabin Medical Center).. Cell Harvest and Culture Conditions. Isolation of human liver cells was performed as described (19). Briefly, liver samples were cut into thin slices (1- to 2-mm thickness), and digested by 0.03% collagenase ...
Understanding the mechanisms underlying beta-cell failure in diabetes constitutes a fundamental challenge for diabetes research. Beta-cell stress and dysfunction contributes to diabetes in both type 1 and type 2 diabetes. In this project, we are exploring the regulatory functions of intermediate filament keratins in pancreatic beta-cell biology under basal circumstances as well in diabetes. It is wellknown that mutations in keratins cause or predispose to many human liver and skin diseases, but the involvement of keratins in diabetes or in beta-cell biology is still insufficiently known. Our earlier research indicates that keratins participate in maintaining blood glucose regulation, beta-cell protein targeting, mitochondrial function and insulin content. Reduced keratin 8 levels moreover increases murine diabetes susceptibility, and early diabetes development is accompanied by keratin upregulation in the pancreatic beta-cells. Pancreatic keratins are thus involved in essential beta-cell ...
The current study demonstrates that overweight/obese adolescents meeting the ADA HbA1c diagnostic criteria (2) for prediabetes have evidence of impaired β-cell function relative to insulin sensitivity, a metabolic signal for heightened risk of type 2 diabetes (27). This finding persisted after adjustment for race and for the greater adiposity in the youth with elevated HbA1c. These data support our hypothesis that alterations in the pathophysiologic mechanisms of type 2 diabetes are evident in the ADA-recommended at-risk/prediabetes category (HbA1c 5.7 to ,6.5%).. Since the release of the HbA1c-based diagnostic criteria for prediabetes/diabetes by the ADA in 2010 (2), reports of adults and some in pediatrics have concluded that HbA1c is inferior to glycemic measures for diagnostic purposes (4-6,11). These studies evaluated the diagnostic sensitivity and specificity of HbA1c compared with glycemic measures, treating the latter as the gold standard. One such study determined that the inferior ...
A study in Cell Stem Cell demonstrates that a gene therapy approach can lead to the long-term survival of functional beta cells as well as normal blood glucose levels for an extended period of time in mice with type 1 diabetes. The researchers used an adeno-associated viral (AAV) vector to deliver to the mouse pancreas two proteins, Pdx1 and MafA, which reprogrammed plentiful alpha cells into functional, insulin-producing beta cells.
Search PubMed for more publications by Alan Attie. Kreznar JH, Keller MP, Traeger LL, Rabaglia ME, Schueler KL, Stapleton DS, Zhao W, Vivas EI, Yandell BS, Broman AT, Hagenbuch B, Attie AD, Rey FE. Host Genotype and Gut Microbiome Modulate Insulin Secretion and Diet-Induced Metabolic Phenotypes. Cell Rep 2017; 18:1739-1750. Attie AD, Churchill GA, Nadeau JH. How mice are indispensable for understanding obesity and diabetes genetics. Current Opinion in Endocrinology Diabetes and Obesity 2017; 24:83-91. Tian J, Keller MP, Broman AT, Kendziorski C, Yandell BS, Attie AD, Broman KW. The Dissection of Expression Quantitative Trait Locus Hotspots. Genetics 2016; 202:1563-1574. Paul PK, Rabaglia ME, Wang CY, Stapleton DS, Leng N, Kendziorski C, Lewis PW, Keller MP, Attie AD. Histone chaperone ASF1B promotes human beta-cell proliferation via recruitment of histone H3.3. Cell Cycle 2016; 15:3191-3202. Krautkramer KA, Kreznar JH, Romano KA, Vivas EI, Barrett-Wilt GA, Rabaglia ME, Keller MP, Attie AD, Rey ...
Importantly, SIX3 and SIX2 are not expressed in mouse beta cells.. This is why it is so important to study human tissue, said Kim. Until now there has been no way of knowing the gradual changes that happen over a period of years.. Kim and his colleagues are planning to continue their studies of pancreatic and islet-cell development as part of a Stanford focus on diabetes and metabolism research. The researchers also anticipate that their gene expression data and newly described islet-cell isolation technique, coupled with the ongoing tissue procurement effort, will be helpful to others studying pancreatic development and diabetes.. This is a unique and valuable resource for researchers wishing to begin to understand how gene expression is dynamically regulated in human islet cells, said Kim. Our study charts a new road map for researchers working to use stem cells to replace human islet cells by highlighting changes that normally occur and should perhaps be taken into consideration when ...
The actions of thyroid hormone (TH) on pancreatic beta cells have not been thoroughly explored, with current knowledge being limited to the modulation of insulin secretion in response to glucose, and beta cell viability by regulation of pro-mitotic and pro-apoptotic factors. Therefore, the effects of TH on proinsulin gene expression are not known. This led us to measure: a) proinsulin mRNA expression, b) proinsulin transcripts and eEF1A protein binding to the actin cytoskeleton, c) actin cytoskeleton arrangement, and d) proinsulin mRNA poly(A) tail length modulation in INS-1E cells cultured in different media containing: i) normal fetal bovine serum - FBS (control); ii) normal FBS plus 1 M or 10 nM T3, for 12 h, and iii) FBS depleted of TH for 24 h (Tx). A decrease in proinsulin mRNA content and attachment to the cytoskeleton were observed in hypothyroid (Tx) beta cells. The amount of eEF1A protein anchored to the cytoskeleton was also reduced in hypothyroidism, and it is worth mentioning that ...
Numerous studies have delineated the transcription factor network that guides beta-cell development and ensures proper beta-cell function by maintaining the fully differentiated state of the cells. To study whether the impaired GSIS observed in Pdx1-CreER;CLEG2;Kif3af/f mice was a result of the loss of the mature beta-cell phenotype, the authors analyzed the expression levels of such factors. Transgenic islets expressed lower levels of Pdx1, as shown by significant reduction of both transcript and protein levels compared with nontransgenic control. The analysis further revealed significant reduction in the expression of MafA, NeuroD1, Nkx6.1, and Neurogenin3 (Ngn3) in transgenic islets 4 wk after TAM treatment compared with control. Thus, elevated Hh signaling causes reduction of critical beta-cell markers, suggesting a loss of the mature beta-cell phenotype ...
Genentech, a bioscience firm famous for its development of antibodies designed to combat cancer, has entered a $350 million agreement with Bayhill Therapeutics to assist in development of BHT-3021, a drug that treats type 1 diabetes by reducing or stopping immune system attacks on pancreatic beta cells.. Under the agreement, Genentech will pay $25 million in upfront to acquire an equity stake in Bayhill, plus another $325 million to finance development of BHT-3021.. Bayhills drug is based on its BHT-DNA antigen-specific immunomodulatory platform. Put simply, the drug has worked in trials by preventing T cells, the bodys immune systems soldiers from mistakenly attacking insulin-producing pancreatic islet cells.. Its done by inserting the gene for a protein that is a known target of the autoimmune system into a plasmid. (A plasmid is a small unit of DNA within a cell that can replicate itself independently of chromosomal DNA). In type 1s, the protein in question is proinsulin.. When the ...
The beta-cells of the pancreatic islets are the unique source of insulin, the main hormone for control of blood glucose and its use as an energy source in the body. A reduction in functional beta cell mass, either due to autoimmunity or prolonged insulin resistance, is a common denominator of different forms of diabetes mellitus.. Hence, a main goal of the CRTD is to protect and replace pancreatic islets in order to prevent and cure diabetes. The research is organized under the themes: ...
CD36 is increased in human islets from obese type 2 diabetes donors, and affects beta cell function by the modulation of exocytotic proteins and insulin content ...
Pancreatic beta cells help maintain normal blood glucose levels by producing the hormone insulin - the master regulator of energy (glucose). Impairment and the loss of beta cells interrupts insulin production, leading to type 1 and 2 diabetes. Using single-cell RNA sequencing, researchers at University of California San Diego School of Medicine have, for the first time, mapped out pathways that regulate beta cell growth that could be exploited to trick them to regenerate.
This Mouse Insulin (INS) ELISA kit is for the quantitative determination of Mouse Insulin concentrations in serum, plasma, cell culture supernates, tissue homogenates, cell lysates. 69+ citations.
Video created by University of Copenhagen for the course Diabetes - a Global Challenge. Inflammatory beta-cell destruction in diabetes by professor Thomas Mandrup-Poulsen. During this module we Professor Mandrup-Poulsen will guide you through ...
The ER stress in the beta cell has been implicated in type 2 diabetes, but its role in triggering beta cell dysfunction in type 1 diabetes has not been clear until now, which is why these findings are exciting, said Dr. Mirmira. Although the paper does not directly address a potential role for ER stress in the development of human T1D, what we observed in the mice is consistent with clinical observations of type 1 diabetes in people where defects in insulin secretion precede overt diabetes.. We need to look more closely at beta cells and their role in type 1 diabetes because they may be participating in their own demise, said Andrew Rakeman, Ph.D. Senior Scientist of Regeneration for JDRF. This study shows that beta cell stress is occurring at the earliest stages of the disease process, raising the intriguing possibility that beta cell stress could be part of the trigger for the autoimmune process that leads to type 1 diabetes. This is exciting because it not only teaches us something ...
Nuestros profesionales publican en revistas científicas de alto impacto con el objetivo de ofrecer a nuestros pacientes los últimos tratamientos. Clínica Universidad de Navarra.
HAMBURG, Germany , Dec. 15, 2010 (GLOBE NEWSWIRE) -- Evotec AG (Frankfurt:EVT) today announced that via its subsidiary Develogen AG it has entered into a license and collaboration agreement with MedImmune (the global biologics unit of AstraZeneca), in the diabetes therapeutic area, with a particular focus on the regeneration of insulin producing beta cells. The license gives MedImmune exclusive access to a portfolio of research programs and represents the first deal executed by Evotec on beta cell regeneration assets and capabilities.
Neogenesis, the differentiation of islet beta cells from progenitor cells present in the pancreas, can continue into postnatal life, and has been reported to occur in several animal models. Recent studies have also demonstrated neogenesis of endocrine cells in vitro from ductal structures or from islet themselves derived from adult human and animals, suggest new possibilities for generating new beta cells in culture. Such strategies might provide models to study the regulation of islet differentiation as well as providing new sources of beta cells for transplantation, but the nature of endocrine progenitors identity and the signals that regulate neogenic activity need to be elucidated. The research focus in my laboratory are: (i) the molecular events controlling pre- and postnatal beta-cell development and maturation, and (ii) the characterization of optimal culture environments for inducing progenitors to differentiate into insulin-producing islet cells, maintaining islet architecture and ...
Type 2 Diabetes Mellitus is the most common type of diabetes, accounting for more than 98% of all cases. Diabetes is intolerance to glucose: a person with diabetes is unable to utilise the glucose present in the blood and so its level remains high, in turn causing several problems. This failure to utilise glucose results from inadequate secretion of the hormone insulin, in turn resulting from failure of beta cells of the pancreas to secrete enough quantities of the hormone in response to a carb rich meal. It can also be due to inefficient action of insulin due to less responsive receptors. Ever increasing evidence suggests that beta cell failure and receptor resistance result from recurrent and prolonged increase in insulin secretion caused by high carbohydrate meals. High carb-high insulin production-insulin resistance-higher insulin production-exhaustion-failure.. At present, the drugs used for treating type 2 diabetes act by reducing receptor resistance and by increasing secretion of insulin ...
N was measured employing Mercodia ultrasensitive mouse insulin ELISA. Glucose was measured working with QuantiChrom Glucose Assay. Body weight and food
Ultra sensitive Mouse Insulin ELISA is an immunoassay for quantitative determination of insulin in mouse serum, plasma and fluid.
Promoting ectopic development of pancreatic beta cells from other cell types is one of the strategies being pursued for the treatment of diabetes. To achieve this, a detailed outline of the molecular lineage that operates in pancreatic progenitor cells to generate beta cells over other endocrine cell types is necessary. Here, we demonstrate that early transient expression of the endocrine progenitor bHLH protein Neurogenin 3 (Ngn3) favors the promotion of pancreatic beta and delta cell fates over an alpha cell fate, while later transient expression promotes ectopic development of all three endocrine cell fates. We found that short-term activation of Ngn3 in Xenopus laevis endoderm just after gastrulation was sufficient to promote both early and ectopic development of beta and delta cells. By examining gene expression changes 4 h after Ngn3 activation we identified several new downstream targets of Ngn3. We show that several of these are required for the promotion of ectopic beta cells by Ngn3 as ...
A new study has shown conclusively that a neuropeptide, melanin concentrating hormone (MCH), found in the brain and known for its role in increasing appetite in people, plays a role in the growth of insulin-producing beta cells and the secretion of insulin.
J:127412 Nir T, Melton DA, Dor Y, Recovery from diabetes in mice by beta cell regeneration. J Clin Invest. 2007 Sep;117(9):2553-61 ...
Goehring, I.; Sauter, N. S.; Catchpole, G.; Assmann, A.; Shu, L.; Zien, K. S.; Moehlig, M.; Pfeiffer, A. F. H.; Oberholzer, J.; Willmitzer, L. et al.; Spranger, J.; Maedler, K.: Identification of an intracellular metabolic signature impairing beta cell function in the rat beta cell line INS-1E and human islets (vol 54, pg 2584, 2011). Diabetologia 62 (3), pp. 553 - 554 (2019 ...
In the case of my autoimmune diabetes (LADA), Ive lost the first phase insulin response. My beta cells will still make some insulin after I eat, but...
Objective: Interleukin (IL)-1 impairs insulin secretion and induces beta-cell apoptosis. Pancreatic beta-cell IL-1 expression is increased and interleukin-1-receptor antagonist (IL-1Ra) expression reduced in patients with type 2 diabetes mellitus. Treatment with recombinant IL-1Ra improves glycemia and beta-cell function and reduces inflammatory markers in patients with type 2 diabetes mellitus. Here we investigated the durability of these responses.. Research Design and Methods: Among 70 ambulatory patients with type 2 diabetes and A1C and body mass index higher than 7.5% and 27, respectively, randomly assigned to receive 13 weeks of anakinra, a recombinant human IL-1Ra, or placebo, 67 completed treatment and were included in this double-blinded 39 week follow-up study. Primary outcome was change in betacell function following anakinra withdrawal. Analysis was done by intention-to-treat.. Results: Thirty-nine weeks following anakinra withdrawal the proinsulin to insulin (PI/I) ratio but not ...
Researchers at the University of California, San Diego School of Medicine have identified a previously unknown biological mechanism involved in the regulation of pancreatic islet beta cells, whose role is to produce and release ...
I thought this an interesting article i would pass on. Transplants of insulin-producing cells from pigs could provide a diabetes cure within a decade, scientists say. http://news.bbc.co.uk/2/hi/hea...
... such as in the insulin-secreting pancreatic beta cells, epithelium, and many other cells. Since CICR is a positive-feedback ... Islam MS, Rorsman P, Berggren PO (January 1992). "Ca(2+)-induced Ca2+ release in insulin-secreting cells". FEBS Letters. 296 (3 ... It is now obvious that CICR is a widely occurring cellular signaling process present even in many non-muscle cells, ... The result of CICR across the cell causes the significant increase in cytosolic Ca2+ that is important in activating muscle ...
Bonny C, Nicod P, Waeber G (March 1998). "IB1, a JIP-1-related nuclear protein present in insulin-secreting cells". J Biol Chem ... RE1-silencing transcription factor (REST) is reported to repress the expression of this gene in insulin-secreting beta cells. ... 2000). "IB1 reduces cytokine-induced apoptosis of insulin-secreting cells". J. Biol. Chem. 275 (22): 16466-72. doi:10.1074/jbc. ... 2001). "Cell-permeable peptide inhibitors of JNK: novel blockers of beta-cell death". Diabetes. 50 (1): 77-82. doi:10.2337/ ...
Rerup CC (1970). "Drugs producing diabetes through damage of the insulin secreting cells". Pharmacol Rev. 22 (4): 485-518. PMID ... In the mid-1960s, streptozotocin was found to be selectively toxic to the beta cells of the pancreatic islets, the cells that ... This explains its relative toxicity to beta cells, since these cells have relatively high levels of GLUT2. Streptozotocin was ... is a naturally occurring alkylating antineoplastic agent that is particularly toxic to the insulin-producing beta cells of the ...
... and insulin-secreting cells (PhD thesis). Uppsala University. CS1 maint: discouraged parameter (link) The value of the Canada ... Rorsman, P.; Renstrom, E. (2003). "Insulin granule dynamics in pancreatic beta cells". Diabetologia. 46 (8): 1029-45. doi: ... Patrik's work also covers human islet cells, which has revealed important differences between ß-cells in man and experimental ... "Calcium-independent potentiation of insulin release by cyclic AMP in single β-cells". Nature. 363 (6427): 356-358. doi:10.1038/ ...
Pancreatic β cells synthesize and secrete insulin to regulate blood glucose levels. One study found that inhibition of OGA with ... cells. PDAC cells have some dependency upon O-GlcNAc for survival as OGT knockdown selectively inhibited PDAC cell ... In a later study, insulin stimulation of COS-7 cells caused OGT to localize to the plasma membrane. Inhibition of PI3K with ... Increasing O-GlcNAc levels by subjecting cells to high glucose conditions or PUGNAc treatment inhibited insulin-stimulated ...
"Interleukin-1beta activates a short STAT-3 isoform in clonal insulin-secreting cells". FEBS Lett. 442 (1): 57-60. doi:10.1016/ ... Cell. Biol. 21 (14): 4544-52. doi:10.1128/MCB.21.14.4544-4552.2001. PMC 87113. PMID 11416133. Radons J, Gabler S, Wesche H, et ... Cell Biol. ENGLAND. 2 (6): 346-51. doi:10.1038/35014038. ISSN 1465-7392. PMID 10854325. S2CID 32036101. Huang, J; Gao X; Li S; ... Cell. Biol. 19 (7): 4798-805. doi:10.1128/mcb.19.7.4798. PMC 84278. PMID 10373529. Jensen LE, Muzio M, Mantovani A, Whitehead ...
25b isoforms are both expressed in insulin-secreting cells and can function in insulin secretion". The Biochemical Journal. 339 ... "Membrane localization and biological activity of SNAP-25 cysteine mutants in insulin-secreting cells". Journal of Cell Science ... doi:10.1016/j.cell.2005.08.029. hdl:11858/00-001M-0000-0010-8592-0. PMID 16169070. S2CID 8235923. Rual JF, Venkatesan K, Hao T ... Molecular Cell Biology. 3 (7): 498-508. doi:10.1038/nrm855. PMID 12094216. S2CID 12384262. Archived from the original (PDF) on ...
"Membrane localization and biological activity of SNAP-25 cysteine mutants in insulin-secreting cells". Journal of Cell Science ... Cell. 122 (6): 957-68. doi:10.1016/j.cell.2005.08.029. hdl:11858/00-001M-0000-0010-8592-0. PMID 16169070. S2CID 8235923. Hata Y ... Putative role in insulin-dependent movement of GLUT-4". The Journal of Biological Chemistry. 272 (10): 6179-86. doi:10.1074/jbc ... The Journal of Cell Biology. 117 (3): 531-8. doi:10.1083/jcb.117.3.531. PMC 2289450. PMID 1315316. McMahon HT, Missler M, Li C ...
Andress DL, Birnbaum RS (1991). "A novel human insulin-like growth factor binding protein secreted by osteoblast-like cells". ... Ilvesmäki V, Blum WF, Voutilainen R (1994). "Insulin-like growth factor binding proteins in the human adrenal gland". Mol. Cell ... Insulin-like growth factor-binding protein 5 is a protein that in humans is encoded by the IGFBP5 gene. An IGFBP5 gene was ... Kiefer MC, Ioh RS, Bauer DM, Zapf J (1991). "Molecular cloning of a new human insulin-like growth factor binding protein". ...
... "islet cell adenoma". Beta cells secrete insulin in response to increases in blood glucose. The resulting increase in insulin ... An insulinoma is a tumor of the pancreas that is derived from beta cells and secretes insulin. It is a rare form of a ... In contrast, the secretion of insulin by insulinomas is not properly regulated by glucose, and the tumors continue to secrete ... Streptozotocin is used in islet cell carcinomas which produce excessive insulin. Combination chemotherapy is used, either ...
2003). "Pancreatic-derived factor (FAM3B), a novel islet cytokine, induces apoptosis of insulin-secreting beta-cells". Diabetes ... Stem cell transplantation was pioneered using bone-marrow-derived stem cells by a team at the Fred Hutchinson Cancer Research ... Hematopoietic stem cell transplantation (HSCT) is the transplantation of blood stem cells derived from the bone marrow (that is ... Islet cell transplantation has the possibility of restoring beta cells and curing diabetes. The Chicago Project headed at ...
April 1996). "Ciclazindol inhibits ATP-sensitive K+ channels and stimulates insulin secretion in CR1-G1 insulin-secreting cells ...
... localization and functional role of small GTPases of the Rab3 family in insulin-secreting cells". Journal of Cell Science. 109 ... "Expression and polarized targeting of a rab3 isoform in epithelial cells". The Journal of Cell Biology. 125 (3): 583-94. doi: ... Weber E, Jilling T, Kirk KL (March 1996). "Distinct functional properties of Rab3A and Rab3B in PC12 neuroendocrine cells". The ... Weber E, Jilling T, Kirk KL (March 1996). "Distinct functional properties of Rab3A and Rab3B in PC12 neuroendocrine cells". The ...
... an islet specific cytokine inducing cell death of insulin-secreting beta cells". Biochemistry. 44 (34): 11342-52. doi:10.1021/ ... in pancreatic beta-cells". Diabetes. 54 (11): 3217-28. doi:10.2337/diabetes.54.11.3217. PMID 16249448. Yang J, Gao Z, Robert CE ...
This is stored with insulin in secretory granules in B cells and is co secreted with insulin." (Rang and Dale's Pharmacology, ... AL is the most common form of amyloidosis, and a diagnosis often begins with a search for plasma cell dyscrasia, memory B cells ... "Searching for the Secrets of the Super Old". Science. 26 September 2008. pp. 1764-1765. Archived from the original on 9 March ... The vast majority of proteins that have been found to form amyloid deposits are secreted proteins, so the misfolding and ...
"Insulin receptor substrate 1 regulation of sarco-endoplasmic reticulum calcium ATPase 3 in insulin-secreting beta-cells". J. ... 1994). "A sarco/endoplasmic reticulum Ca2+-ATPase 3-type Ca2+ pump is expressed in platelets, in lymphoid cells, and in mast ... 2006). "Sarco/endoplasmic reticulum Ca2+ATPase type 3 isoforms (SERCA3b and SERCA3f): distinct roles in cell adhesion and ER ... 2002). "Expression of endomembrane calcium pumps in colon and gastric cancer cells. Induction of SERCA3 expression during ...
Adiponectin: is a type of protein secreted by adipose cells that improves insulin sensitivity and possesses antiatherogenic ... The blood cells in sickle cell disease are abnormally shaped (sickle-shaped) and may form clots or block blood vessels. ... Interleukin-6 is an interleukin (type of protein) produced by T-cells (specialized white blood cells), macrophages and ... Sickle cell anemia: is an autosomal recessive genetic blood disorder caused in the gene (HBB gene) which codes for hemoglobin ( ...
... "miR-375 enhances palmitate-induced lipoapoptosis in insulin-secreting NIT-1 cells by repressing myotrophin (V1) protein ... It has been used in miR fluorescence in situ hybridization to distinguish Merkel cell polyomavirus-positive Merkel cell ... miR-375 knockout mice have decreased numbers of β-cells and increased numbers of α-cells. The increase in glucagon levels, ... "MiR-375 frequently downregulated in gastric cancer inhibits cell proliferation by targeting JAK2". Cell Res. 20 (7): 784-793. ...
GLP-1 is a hormone that helps pancreatic beta cells to secrete insulin in response to high blood sugar. Because it works like ... insulin is only secreted when blood sugar is high. Like GLP-1, it also slows gastric emptying. Lixisenatixe is a peptide made ... Use with insulin or sulfonylurea may cause hypoglycemia. In some cases, people with no kidney disease have had acute kidney ... In the European Union, its use is limited to complementing insulin therapy. As of 2017 it is unclear if they affect a person's ...
"The antiepileptic drug topiramate preserves metabolism-secretion coupling in insulin secreting cells chronically exposed to the ... Kim J, Kondratyev A, Gale K (October 2007). "Antiepileptic drug-induced neuronal cell death in the immature brain: effects of ... August 2007). "Effects of lamotrigine alone and in combination with MK-801, phenobarbital, or phenytoin on cell death in the ... December 2011). "Pattern of antiepileptic drug-induced cell death in limbic regions of the neonatal rat brain". Epilepsia. 52 ( ...
... an atypical isoform of protein kinase C derived from insulin-secreting cells". The Journal of Biological Chemistry. 268 (32): ... Ruegg CL, Strand M (May 1990). "Inhibition of protein kinase C and anti-CD3-induced Ca2+ influx in Jurkat T cells by a ... Kohjima M, Noda Y, Takeya R, Saito N, Takeuchi K, Sumimoto H (Dec 2002). "PAR3beta, a novel homologue of the cell polarity ... Fields AP, Bednarik DP, Hess A, May WS (May 1988). "Human immunodeficiency virus induces phosphorylation of its cell surface ...
Diazoxide is a medication used to primarily reduce the excess insulin secreted from the insulinoma cells. Insulin is suppressed ... The excess insulin secretes into the blood stream and causes a significant drop in the blood glucose level, also known as ... An insulinoma is a small tumor localized to the pancreas, originating from islet beta cells, which produce an excess of insulin ... from excess insulin secretion from the islet beta cells within the pancreatic tumor or from non-pancreatic tumor cells. ...
... of islet cell tumors originate from a β-cell, secrete insulin (insulinoma), and can cause fasting hypoglycemia. β-cell tumors ... Most islet cell tumors secrete pancreatic polypeptide, the clinical significance of which is unknown. Gastrin is secreted by ... These genetic changes result in no functional copies of the MEN1 gene in selected cells, allowing the cells to divide with ... Pancreatic islet cell tumors are today the major cause of death in persons with MEN-1. Tumors occur in 60-80% of persons with ...
... of a third pituitary adenylate cyclase-activating polypeptide receptor subtype expressed in insulin-secreting cells". Proc. ... Felley, C P; Qian J M; Mantey S; Pradhan T; Jensen R T (Dec 1992). "Chief cells possess a receptor with high affinity for PACAP ... 1993). "Chief cells possess a receptor with high affinity for PACAP and VIP that stimulates pepsinogen release". Am. J. Physiol ... In addition, it plays a role in paracrine and autocrine regulation of certain types of cells. This gene is composed of five ...
The NR4A1 gene is a transcription factor important in the development of cells that secrete the hormone insulin-like 3 (INSL3 ... In the male reproductive system the NR4A1 gene is a promoter of insulin-like 3 in Leydig cells. Leydig cells are located in the ... It is secreted by thecal and luteal cells in the ovary and thus is important in the maturation of developing oocytes. In the ... Tremblay The Orphan Nuclear Receptor NR4A1 Regulates Insulin-Like 3 Gene Transcription in Leydig Cells Biol Reprod February ...
However, data showing that HMR 1098 inhibits the Kir6.2/SUR1 KATP subtype found in insulin-secreting pancreatic beta cells ... In particular its interaction with coronary smooth muscle cells and pancreatic-β cells cause decreased coronary blood flow, ... Cell. Cardiol. 50(3):552-560 Wilde, A. A. M. (1993). Role of ATP-sensitive K+ channel current in ischemic arrhythmias. ... Hypoxia provokes potassium efflux from cardiac muscles cells via the activation of ATP-sensitive potassium channels (KATP). ...
Insulin is a polypeptide hormone secreted by cells in the islets of Langerhans, which are contained throughout the pancreas. ... Insulin also exhibits vasodilatory properties. In normotensive individuals, insulin may stimulate sympathetic activity without ... Renin is an enzyme secreted by the juxtaglomerular apparatus of the kidney and linked with aldosterone in a negative feedback ... Also, the water movement between cells and the interstitium plays a minor role compared to this.[citation needed] Excessive ...
Andress DL, Birnbaum RS (1991). "A novel human insulin-like growth factor binding protein secreted by osteoblast-like cells". ... Ilvesmäki V, Blum WF, Voutilainen R (1994). "Insulin-like growth factor binding proteins in the human adrenal gland". Mol. Cell ... 1999). "Insulin-like growth factors (IGF-I, free IGF-I and IGF-II) and insulin-like growth factor binding proteins (IGFBP-2, ... 1995). "A human keratinocyte cell line produces two autocrine growth inhibitors, transforming growth factor-beta and insulin- ...
Although transplant rejection remains a problem, recent clinical trials that involved implanting pig insulin-secreting cells ... Collins FS, Rossant J, Wurst W (2007). "A mouse for all reasons". Cell. 128 (1): 9-13. doi:10.1016/j.cell.2006.12.018. PMID ... Insulin was first isolated from dogs in 1922, and revolutionized the treatment of diabetes. On 3 November 1957, a Soviet dog, ... In the case of C. elegans, the worm's body is completely transparent and the precise lineage of all the organism's cells is ...
... cells, beta (B) cells, Delta (D) cells and F cells. Glucagon is secreted from alpha cells, while insulin is secreted by beta ... The lower blood-glucose level (a product of the insulin secretion) triggers glucagon to be secreted, and repeats the cycle. In ... insulin), which decreases blood glucose. These hormones are secreted from pancreatic islets (bundles of endocrine tissues), of ... Because red blood cells (erythrocytes) have a higher concentration of protein (e.g., hemoglobin) than serum, serum has a higher ...
The brain detects insulin in the blood, which indicates that nutrients are being absorbed by cells and a person is getting full ... The hormone cholecystokinin is secreted by the duodenum, and it controls the rate at which the stomach is emptied.[23] This ... Peptide YY 3-36 is a hormone released by the small intestine and it is also used as a satiety signal to the brain.[24] Insulin ... Adipose tissue secretes the hormone leptin, and leptin suppresses appetite. Long-term satiety signals from adipose tissue ...
... comparable to insulin action in vitro.». British journal of biomedical science. ... In vitro modulation of oxidative burst via release of reactive oxygen species from immune cells by extracts of selected ... https://www.ted.com/talks/ameenah_gurib_fakim_humble_plants_that_hide_surprising_secrets?language=en ...
... and Th1 cells.[45] IL-1α stimulates increased skin cell activity and reproduction, which, in turn, fuels comedo development.[45 ... High levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are also associated with worsened acne.[42] Both ... The adrenal glands secrete higher amounts of DHEA-S during adrenarche (a stage of puberty), and this leads to an increase in ... and accumulation of skin cells in the hair follicle.[1] In healthy skin, the skin cells that have died come up to the surface ...
... is a synthetic form of thyroxine (T4), an endogenous hormone secreted by the thyroid gland, which is converted to ... its active metabolite, L-triiodothyronine (T3).[20] T4 and T3 bind to thyroid receptor proteins in the cell nucleus and cause ... metabolic effects through the control of DNA transcription and protein synthesis.[20] Like its naturally secreted counterpart, ...
Fuentes would run the blood through a centrifuge, separating the blood plasma from the red blood cells. The cells would be re- ... It described intake of EPO, growth hormones, testosterone and insulin on 114 days during the 200-day season of 2003.[53] ... The Spanish authorities lifted the secret of summary two days before the start of the 2006 Tour, formally involving all 56 ... If haematocrit levels (volume of red blood cells) got dangerously high, they would re-inject plasma as well, enhanced with EPO ...
Endocrine glands are the cardinal example, but speicialised cells in various ither organs an aw secrete hormones. Hormone ... Some hormones are completely active whan released intae the bluidstream (as is the case for insulin an growthe hormones), while ... Hormones affect distant cells bi bindin tae speceefic receptor proteins in the target cell resultin in a chynge in cell ... The term hormone is whiles extendit tae include chemicals produced bi cells that affect the same cell (autocrine or intracrine ...
cell-cell signaling. • positive regulation of brain-derived neurotrophic factor receptor signaling pathway. • collateral ... BDNF is made in the endoplasmic reticulum and secreted from dense-core vesicles. It binds carboxypeptidase E (CPE), and the ... Insulin-like growth factor-1 (somatomedin C). *IGF-1 LR3. *Insulin-like growth factor-2 (somatomedin A) ... regulation of protein localization to cell surface. • regulation of receptor activity. • activation of phospholipase C activity ...
... animal and human cells and its re-expression triggered beta cell proliferation and corrected glucose regulation via insulin ... All PDGFs function as secreted, disulphide-linked homodimers, but only PDGFA and B can form functional heterodimers. ... PDGF[1][2] is a potent mitogen for cells of mesenchymal origin, including fibroblasts, smooth muscle cells and glial cells. In ... "Cell Death and Control of Cell Survival in the Oligodendrocyte Lineage". Cell. 70 (1): 31-46. doi:10.1016/0092-8674(92)90531-G ...
positive regulation of heterotypic cell-cell adhesion. • negative regulation of mitotic cell cycle. • endothelial cell ... The secreted form of human TNFα takes on a triangular pyramid shape, and weighs around 17-kDa. Both the secreted and the ... It also induces insulin resistance by promoting serine-phosphorylation of insulin receptor substrate-1 (IRS-1), which impairs ... but it is produced also by a broad variety of cell types including lymphoid cells, mast cells, endothelial cells, cardiac ...
The endocrine part secretes insulin when the blood sugar becomes high; insulin moves glucose from the blood into the muscles ... These include the various cells of the gastric glands, taste cells, pancreatic duct cells, enterocytes and microfold cells. ... Gastric lipase secreted by the chief cells in the fundic glands in the gastric mucosa of the stomach, is an acidic lipase, in ... Smaller amounts of lipase and amylase are secreted. The pancreas also secretes phospholipase A2, lysophospholipase, and ...
O'Dell SD, Day IN (Jul 1998). "Insulin-like growth factor II (IGF-II)". The International Journal of Biochemistry & Cell ... The MeSH definition reads: "A well-characterized neutral peptide believed to be secreted by the liver and to circulate in the ... insulin receptor binding. • hormone activity. • GO:0001948 protein binding. • growth factor activity. • insulin-like growth ... Insulin-like growth factor 2 (IGF-2) is one of three protein hormones that share structural similarity to insulin. ...
These can be macrophages that secrete IL-12, which stimulates the proliferation of further CD4+ Th1 cells. CD4+ T cells secrete ... Pancreatic beta cell proteins (possibly insulin, glutamate decarboxylase). Insulitis, beta cell destruction. ... These cells differentiate into epithelioid cells which wall off the infected cells, but results in significant inflammation and ... Walled off lesion containing macrophages and other cells. Some peripheral neuropathies. Schwann cell antigen. Neuritis, ...
When oxytocin binds to the myoepithelial cells, the cells contract. The increased intra-aveolar pressure forces milk into the ... The single egg of the tse-tse develops into a larva inside the uterus where it is fed by a milky substance secreted by a milk ... High levels of prolactin during pregnancy and breastfeeding also increase insulin resistance, increase growth factor levels ( ... called tract cells, in the posterior dorsal horn. The tract cells then decussate via the anterior white commissure to the ...
... to or the availability of critical secreted growth factors that are necessary to maintain muscle mass and satellite cell ... insulin resistance and dyslipidaemia". Diabetes, obesity & metabolism. 7 (4): 406-13. PMID 15955127. doi:10.1111/j.1463- ... The threadlike muscle fibers are the individual muscle cells (myocytes), and each cell is encased within its own endomysium of ... In one line of thought scientists have believed that muscle cells evolved once and thus all animals with muscles cells have a ...
Many proteins are involved in the process of cell signaling and signal transduction. Some proteins, such as insulin, are ... Antibodies can be secreted into the extracellular environment or anchored in the membranes of specialized B cells known as ... Other proteins are important in cell signaling, immune responses, cell adhesion, and the cell cycle. In animals, proteins are ... Abundance in cells. It has been estimated that average-sized bacteria contain about 2 million proteins per cell (e.g. E. coli ...
Small cell carcinoma, a common cause of ACTH secreted ectopically. *Congenital adrenal hyperplasia, diseases in the production ... ACTH acts by binding to cell surface ACTH receptors, which are located primarily on adrenocortical cells of the adrenal cortex ... ACTH also stimulates lipoprotein uptake into cortical cells. This increases the bioavailability of cholesterol in the cells of ... POMC, ACTH and β-lipotropin are secreted from corticotropes in the anterior lobe (or adenohypophysis) of the pituitary gland in ...
A fall in blood glucose, causes insulin secretion to be stopped, and glucagon to be secreted from the alpha cells into the ... The sensors for the second are the parafollicular cells in the thyroid gland. The parathyroid chief cells secrete parathyroid ... The beta cells respond to a rise in the blood sugar level by secreting insulin into the blood, and simultaneously inhibiting ... whose numbers in the cell wall are increased as a direct effect of insulin acting on these cells. The glucose that enters the ...
... including small cell lung cancer Tumors that secrete insulin- or insulin-like growth factor 2 Duodenal cancer List of cutaneous ... Mignogna MD, Fortuna G, Satriano AR (December 2008). "Small-cell lung cancer and necrolytic migratory erythema". The New ... swollen epidermal cells and necrosis of the superficial epidermis are most characteristic. Immunofluorescence is usually ...
cell-cell signaling. • ephrin receptor signaling pathway. • axon guidance. • osteoclast differentiation. • bone remodeling. ... 2000). "A splice variant of human ephrin-A4 encodes a soluble molecule that is secreted by activated human B lymphocytes". ... Insulin-like growth factor-1 (somatomedin C). *IGF-1 LR3. *Insulin-like growth factor-2 (somatomedin A) ... Cells. 9 (4): 440-5. PMID 10515610.. *. Aasheim HC, Munthe E, Funderud S, et al. ( ...
Intestinal GLP-2 is co-secreted along with GLP-1 upon nutrient ingestion. ... GLP-2 is produced by the intestinal endocrine L cell and by various neurons in the central nervous system. ... Insulin. *Agonists: Chaetochromin (4548-G05). *Insulin-like growth factor 1. *Insulin-like growth factor 2 ...
It is secreted by mesenchymal cells and targets and acts primarily upon epithelial cells and endothelial cells, but also acts ... Insulin-like growth factor 1. *Epithelial-mesenchymal transition. *Madin-Darby Canine Kidney Cells ... Hepatocyte growth factor is secreted by mesenchymal cells and acts as a multi-functional cytokine on cells of mainly epithelial ... endothelial cells and haemopoietic progenitor cells, HGF also regulates the chemotaxis of T cells into heart tissue. Binding of ...
The thymus also secretes hormones and cytokines that regulate the maturation of T cells, including thymulin, thymopoietin, and ... and drives the transcription of organ-specific genes such as insulin to allow maturing thymocytes to be exposed to a more ... Cells in the thymus can be divided into thymic stromal cells and cells of hematopoietic origin (derived from bone marrow ... Stromal cells include epithelial cells of the thymic cortex and medulla, and dendritic cells. The thymus provides an inductive ...
... they regulate other immune cell functions (e.g., CD4+ T cell, dendritic cell, B cell, mast cell, neutrophil, and basophil ... There is usually a granulocyte chemotactic defect in individuals suffering from insulin-dependent diabetes mellitus. ... Neutrophils can secrete products that stimulate monocytes and macrophages; these secretions increase phagocytosis and the ... Mast cells[edit]. See article: Mast cell. Mast cells are a type of granulocyte that are present in tissues;[3] they mediate ...
... which is secreted from the pituitary gland, and insulin-like growth factor 1 (IGF-1), which is produced in the body in response ... insulin-like growth factor binding protein-3 and epidermal growth factor on human breast epithelial cells in primary culture". ... "The mitogenic action of insulin-like growth factor I in normal human mammary epithelial cells requires the epidermal growth ... "Cell. Signal. 19 (9): 1956-63. doi:10.1016/j.cellsig.2007.05.003. PMC 2681182. PMID 17572069.. ...
... is the movement of material from one point to another, e.g. secreted chemical substance from a cell or gland. In ... More modification can occur in the secretory vesicles (for example insulin is cleaved from proinsulin in the secretory vesicles ... "Unconventional mechanisms of protein transport to the cell surface of eukaryotic cells". Annual Review of Cell and ... Additionally, T4SS also secrete virulence factor proteins directly into host cells as well as taking up DNA from the medium ...
50,000 per SMRT cell, or 500-1000 megabases[69][70]. 30 minutes to 4 hours[71]. $0.13-$0.60. Fast. Detects 4mC, 5mC, 6mA.[72]. ... Sanger's success in sequencing insulin greatly electrified x-ray crystallographers, including Watson and Crick who by now were ... a small protein secreted by the pancreas. This provided the first conclusive evidence that proteins were chemical entities with ... ruled that individuals have no property rights to discarded cells or any profits made using these cells (for instance, as a ...
Thus it was considered to contain the secret of fate and was used for fortune-telling. In Plato, and in later physiology, the ... ಇನ್ಸುಲಿನ್‌-ಸದೃಶ ವರ್ಧನಾಂಶ (insulin-like growth factor-1)ವನ್ನೂ (IGF-1) ಯಕೃತ್ತು ಉತ್ಪಾದಿಸುತ್ತದೆ. ಇದು ಬಾಲ್ಯದಲ್ಲಿನ ಬೆಳವಣಿಗೆಯಲ್ಲಿ ... "p75 Neurotrophin receptor is a marker for precursors of stellate cells and portal fibroblasts in mouse fetal liver" ...
Pulsatile insulin secretion from individual beta cells is driven by oscillation of the calcium concentration in the cells. In ... α and δ cells in the pancreas also share secrete factors in a similar pulsatile manner.[10] ... The most common examples of hormones that are secreted pulsatilely include insulin, thyrotropin, TRH, gonadotropin-releasing ... Pulsatile secretion is a biochemical phenomenon observed in a wide variety of cell types, in which chemical products are ...
The osteoclast then induces an infolding of its cell membrane and secretes collagenase and other enzymes important in the ... Growth hormone is an important regulator of bone growth and remodeling in adults, and it acts via insulin-like growth factor I ... The osteoclasts are multi-nucleated cells that contain numerous mitochondria and lysosomes. These are the cells responsible for ... Low levels of calcium stimulates the release of parathyroid hormone (PTH) from chief cells of the parathyroid gland. In ...
... α-cells and somatostatin-producing δ-cells become insulin-expressing cells after the ablation of insulin-secreting β-cells, ... Notably, insulin-producing α-cells maintain expression of α-cell markers, as seen by deep transcriptomic and proteomic ... Here we show that islet non-β-cells, namely α-cells and pancreatic polypeptide (PPY)-producing γ-cells, obtained from deceased ... When transplanted into diabetic mice, converted human α-cells reverse diabetes and continue to produce insulin even after six ...
... paving the way for a cell therapy to treat diabetes. ... Researchers craft hormone-producing pancreas cells from human ... beta cells. cell & molecular biology. diabetes. human embryonic stem cells. insulin. pancreas. stem cell research. stem cells. ... Lab-Made Insulin-Secreting Cells. Researchers craft hormone-producing pancreas cells from human embryonic stem cells, paving ... And the process yielded billions of the insulin-secreting cells. "Youll be able to create buckets and buckets of cells," ...
Inward currents were measured in cultured rat pancreatic islet cells using the whole-cell patch-clamp technique. Depolarization ... Evidence for two calcium currents in insulin-secreting cells Pflugers Arch. 1988 Apr;411(4):401-9. doi: 10.1007/BF00587719. ... Inward currents were measured in cultured rat pancreatic islet cells using the whole-cell patch-clamp technique. Depolarization ... First, a second shoulder, or hump, was observed on the descending limb of the Ca current I-V of many cells, suggesting that ...
Cell Calcium. 1994 Aug;16(2):71-80. Research Support, Non-U.S. Govt ... Cell Calcium. 1994 Aug;16(2):71-80.. Ca2+ stores in insulin-secreting cells: lack of effect of cADP ribose.. Rutter GA1, Theler ... Ca2+ stores were examined in several insulin secreting cell types by measuring uptake and release of Ca2+ by permeabilised ... caused significant Ca2+ release from any of the permeabilised insulin-secreting cell preparations. ATP elicited similar ...
... non-invasive methods for the characterisation and quantification of beta-cell mass would greatly enhance our means for gaining ... The secret life of insulin-producing cells -The development of sensitive, ... The secret life of insulin-producing cells The insulin-producing cells in the pancreas play a crucial role in the management of ... The secret life of insulin-producing cells The insulin-producing cells in the pancreas play a crucial role in the management of ...
... were established from cells isolated from an x-ray-induced rat transplantable insulinoma. The continuous growth of these cells ... New insulin-secreting cell lines (INS-1 and INS-2) ... New insulin-secreting cell lines (INS-1 and INS-2) were ... Establishment of 2-mercaptoethanol-dependent differentiated insulin-secreting cell lines Endocrinology. 1992 Jan;130(1):167-78. ... The content of immunoreactive insulin was about 8 micrograms/10(6) cells, corresponding to 20% of the native beta-cell content ...
L. Best, R. Trebilcock, S. Tomlinson; 2-Ketoisocaproate transport in insulin-secreting cells. Biosci Rep 1 February 1992; 12 (1 ... In silico approach to predict pancreatic β-cells classically secreted proteins Biosci Rep (February, 2020) ... Addition of 10-30 mM KIC to dispersed islets cells or HIT-T15 cells produced a rapid intracellular acidification. In islets, ... However, in HIT-T15 cells, the rate of uptake of KIC greatly exceeded the oxidation rate. The low rate of KIC oxidation could ...
These results indicate that betacellulin and activin A convert amylase-secreting AR42J cells into cells secreting insulin. ... Betacellulin and activin A coordinately convert amylase-secreting pancreatic AR42J cells into insulin-secreting cells.. ... Betacellulin and activin A coordinately convert amylase-secreting pancreatic AR42J cells into insulin-secreting cells.. ... of the cells became insulin positive. Morphologically, the insulin-positive cells were composed of two types of cells: neuron- ...
The new method, presented in the journal Scientific Reports, can be used to assess insulin resistance during progression and ... researchers at Swedens Karolinska Institutet have developed a novel technique that makes it possible to monitor insulin ... Insulin-secreting cells report on insulin resistance. by Karolinska Institutet Diabetes researchers at Swedens Karolinska ... medicalxpress.com/news/2016-02-insulin-secreting-cells-insulin-resistance.html This document is subject to copyright. Apart ...
However, our βHC9 insulin-secreting cells contained only ∼0.6 pg insulin/cell, whereas the whole mouse islets used by Detimary ... If the cell is well energized, i.e., when KATP channels have low activity, the B-cells release insulin. If the cell is poorly ... We estimated the concentration of free ADP in βHC9 hyperplastic insulin-secreting cells based on the cell diameter and on ... Evidence for creatine kinase activity in βHC9 insulin-secreting cells. βHC9 cells were maintained at room temperature in fuel- ...
Subcellular localization, mobility, and kinetic activity of glucokinase in glucose-responsive insulin-secreting cells.. ... Subcellular localization, mobility, and kinetic activity of glucokinase in glucose-responsive insulin-secreting cells. ... Subcellular localization, mobility, and kinetic activity of glucokinase in glucose-responsive insulin-secreting cells. ... Subcellular localization, mobility, and kinetic activity of glucokinase in glucose-responsive insulin-secreting cells. ...
The number of beta cells in the pancreas increases in response to greater demand for insulin or ... ... the hormone responsible for stimulating cells to convert glucose to energy. ... No rebirth for insulin secreting pancreatic beta cells. April 24, 2013, Journal of Clinical Investigation Pancreatic beta cells ... Researchers discover mechanism that could convert certain cells into insulin-making cells. April 29, 2011 Simply put, people ...
ATP-sensitive K+ channels that are blocked by hypoglycemia-inducing sulfonylureas in insulin-secreting cells are activated by ... ATP-sensitive K+ channels that are blocked by hypoglycemia-inducing sulfonylureas in insulin-secreting cells are activated by ... ATP-sensitive K+ channels that are blocked by hypoglycemia-inducing sulfonylureas in insulin-secreting cells are activated by ... ATP-sensitive K+ channels that are blocked by hypoglycemia-inducing sulfonylureas in insulin-secreting cells are activated by ...
Frequency Therapeutics awarded grant from JDRF International to pursue small molecule approach for beta cell replacement to ... intestinal stem cells into functional insulin-secreting cells using small molecule drugs, which could be a key step in ... Frequency Therapeutics Awarded Grant from JDRF to Generate Glucose-Responsive Insulin-Secreting Cells for Type 1 Diabetes ... gastrointestinal stem cells to differentiate into insulin-producing beta cells, in an effort to discover and develop new ...
In vivomany factors determine the regulation of insulin secretion from the β-cells of the pancreatic islets of Langerhans. The ... However, few studies have examined intracellular Ca2+ signalling in isolated human insulin-secreting cells(4,7-10). In a recent ... In vitro it has been demonstrated using rodent and clonal insulin-secreting cells that purinergic receptor activation is ... voltage-operated calcium channels in insulin-secreting cells. Eur. J. Pharmacol. 216: 407-414.PubMedCrossRefGoogle Scholar ...
Intrinsic optical signal imaging of glucose-stimulated insulin secreting β-cells Yi-Chao Li, Wan-Xing Cui, Xu-Jing Wang, ... In this paper, we demonstrate the feasibility of using IOS imaging for functional examination of insulin secreting INS-1 cells ... "Intrinsic optical signal imaging of glucose-stimulated insulin secreting β-cells," Opt. Express 19, 99-106 (2011) ... 4 (A) Enlarged image of cell 4 in Fig. 3A. The enclosed red line around the cell represents the boundary calculated by the ...
In conclusion, the pancreatic progenitor cells could be differentiated to insulin-secreting islet β-cells by the pregnant serum ... Hormonal manipulation induces differentiation of pancreatic progenitor cells into insulin-secreting islet β-cells. ... also known as pancreatic progenitor cells, could be differentiated into insulin-secreting islet β-cells. In this study, we ... no matter the aggregated cells or the sphere-shaped ones are capable of secreting insulin. ...
... and clinical studies in all areas of stem cell biology and applications. The journal will consider basic, translational, and ... Stem Cells International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, ... Cotransplantation of Adipose Tissue-Derived Insulin-Secreting Mesenchymal Stem Cells and Hematopoietic Stem Cells: A Novel ... "Human adipose-tissue derived mesenchymal stem cells differentiate in to insulin, somatostatin and glucagons expressing cells," ...
Stem cells from diabetic patients coaxed to become insulin-secreting cells. Posted on June 1, 2016. by Vetscite ... "The cells weve manufactured sense the presence of glucose and secrete insulin in response. And beta cells do a much better job ... own stem cells to manufacture new cells that make insulin.. The researchers showed that the new cells could produce insulin ... The scientists tested the cells in culture and in mice, and in both cases found that the cells secreted insulin in response to ...
Culture and Function of Electrofusion-Derived Clonal Insulin-Secreting Cells Immobilized on Solid and Macroporous Microcarrier ... Culture and Function of Electrofusion-Derived Clonal Insulin-Secreting Cells Immobilized on Solid and Macroporous Microcarrier ... Insulin concentration in the culture medium reached a peak of26±2.0 ng/ml and 24±2.2 ng/ml for cells grown oncytodex-1 and ... L-alanine (10 mmol/l) andL-arginine (10 mmol/l) also induced significant 3-4 fold increasesof insulin release. BRIN-BD11 cells ...
Some of the most exciting possibilities aim to replace the function of the insulin-secreting pancreatic beta cells that is ... Can Artificial Cells Take Over for Lost Insulin-Secreting Cells?. Posted on November 7th, 2017. by Dr. Francis Collins ... Some of the most exciting possibilities aim to replace the function of the insulin-secreting pancreatic beta cells that is ... insulin, insulin storage granules, lipids, microneedle skin patches, microneedles, pancreas, pancreatic beta cells, type 1 ...
... from mouse embryonic stem cells, we have developed an optimized 5-stage protocol by... ... In order to produce insulin-secreting cells with a high value of glucose-stimulated insulin secretion (GSIS) ... Glucose-stimulated insulin secretion Insulin-secreting cells Mouse ES cells Pre-diabetes model mice ... Development of an optimized 5-stage protocol for the in vitro preparation of insulin-secreting cells from mouse ES cells. ...
Early Placenta Insulin-like Growth Factor (pro-EPIL) Is Overexpressed and Secreted by c-erbB-2-positive Cells with High ... Early Placenta Insulin-like Growth Factor (pro-EPIL) Is Overexpressed and Secreted by c-erbB-2-positive Cells with High ... Early Placenta Insulin-like Growth Factor (pro-EPIL) Is Overexpressed and Secreted by c-erbB-2-positive Cells with High ... Early Placenta Insulin-like Growth Factor (pro-EPIL) Is Overexpressed and Secreted by c-erbB-2-positive Cells with High ...
Insulin-like Growth Factor I Secreted from Prostate Stromal Cells Mediates Tumor-Stromal Cell Interactions of Prostate Cancer. ... Insulin-like Growth Factor I Secreted from Prostate Stromal Cells Mediates Tumor-Stromal Cell Interactions of Prostate Cancer ... Insulin-like Growth Factor I Secreted from Prostate Stromal Cells Mediates Tumor-Stromal Cell Interactions of Prostate Cancer ... Insulin-like Growth Factor I Secreted from Prostate Stromal Cells Mediates Tumor-Stromal Cell Interactions of Prostate Cancer ...
... adenoviral REST transduction in INS-1E cells led to increased cell death under control conditions, and sensitized cells to ... Using siRNA-mediated knockdown in INS-1E cells, we showed that Cdk5r2 protects beta cells against cytokines and palmitate- ... Decreased levels of Cdk5r2 in beta cells of RIP-REST mice further confirmed that it is controlled by REST, in vivo. ... In diabetic RIP-REST mice, high levels of REST were associated with postnatal beta cell apoptosis, which resulted in gradual ...
Measuring phospholipase D activity in insulin-secreting pancreatic beta-cells and insulin-responsive muscle cells and ... Measuring phospholipase D activity in insulin-secreting pancreatic beta-cells and insulin-responsive muscle cells and ... Measuring phospholipase D activity in insulin-secreting pancreatic beta-cells and insulin-responsive muscle cells and ... in secretagogue-stimulated insulin-secreting pancreatic beta-cells and also insulin-stimulated adipocyte and muscle cells, two ...
... are able to enhance the rate of insulin secretion, both in vivo and in vitro1. 86Rb+... ... A. Remaury, and H. Paris, The insulin-secreting cell line, RINm5F, expresses an alpha-2D adrenoceptor and nonadrenergic ... Identification and Characterization of Non-Adrenergic Binding Sites in Insulin-Secreting Cells with the Imidazoline RX821002. ... ATP channels in insulin-secreting cells, Eur. J. Pharmacol. 204: 41 (1991).PubMedCrossRefGoogle Scholar ...
... developed a new approach to identify expression of low-level enzymes for the first time in primary insulinsecreting beta cells ... β-cells). In their research, they found that these proteins are critical, functional components of key metabolic pathways which ... can support β-cell survival under inflammatory stress. ... Identify low-level enzymes in primary insulin-secreting β-cells ... Proteomic Interrogation of Primary Insulin-Secreting Pancreatic β-cells Application Note Sep 30, 2020 ...
... selective inhibitors on cyclic nucleotide phosphodiesterase activity and insulin secretion in the clonal insulin secreting cell ... selective inhibitors on cyclic nucleotide phosphodiesterase activity and insulin secretion in the clonal insulin secreting cell ... 7. These findings, in a clonal insulin secreting cell line, are consistent with an important role for PDE3B in regulating the ... 1. The cyclic nucleotide phosphodiesterases (PDEs) present in an insulin secreting cell line, BRIN - BD11, were characterized ...
... generation of novel insulin and glucagon secreting islet-like cell clusters from islet-derived non differentiated cells (. ... Obestatin improves in vitro generation of novel insulin and glucagon secreting islet-like cell clusters from islet-derived non ... in vitro generation of novel insulin and glucagon secreting islet-like cell clusters from islet-derived non differentiated ... cells /> in vitro generation of novel insulin and glucagon secreting islet-like cell clusters from islet-derived non ...
  • These cells synthesized both proinsulin I and II and displayed conversion rates of the two precursor hormones similar to those observed in rat islets. (nih.gov)
  • The transport of the nutrient secretagogue 2-ketoisocaproate (KIC) was studied in isolated rat pancreatic islets and in the HIT-T15 insulinoma cell line using an oil-filtration technique. (portlandpress.com)
  • In both islets and HIT-T15 cells, KIC uptake was a slow process, not reaching equilibrium within 10 min KIC transport was not dependent upon Na + in the medium, was not inhibited by α-cyano-4-hydroxy-cinnamate nor by 2-amino-2-norborane carboxylic acid (BCH) and did not appear to be electrogenic. (portlandpress.com)
  • Addition of 10-30 mM KIC to dispersed islets cells or HIT-T15 cells produced a rapid intracellular acidification. (portlandpress.com)
  • In islets, the rate of transport of 10 mM KIC was comparable with oxidation rate of the keto-acid suggesting that uptake could be rate-limiting factor for KIC oxidation and thus stimulated insulin release. (portlandpress.com)
  • A major challenge in the field of insulin resistance is to be able to monitor this process dynamically in individual cell types of insulin target tissues, such as fat, liver, brain, kidney or pancreatic islets in the living organism. (medicalxpress.com)
  • However, by equipping beta-cells with a fluorescent biosensor that reports on insulin resistance and transplanting these reporter islets into the anterior chamber of the eyes of mice, we are now able to study beta-cell insulin sensitivity over months in the living mouse. (medicalxpress.com)
  • The biosensor expressed by the engrafted islets makes it possible for the researchers to differentiate insulin-resistant cells from those that have a normal response to insulin. (medicalxpress.com)
  • In vivo many factors determine the regulation of insulin secretion from the β-cells of the pancreatic islets of Langerhans. (springer.com)
  • These influences are important avenues for β-cell regulation as they not only provide a link between the gastrointestinal tract and the pancreatic islets - the enteroinsular axis , but they also govern the neurohormonal control of secretion. (springer.com)
  • In a recent paper we have shown that ATP and other agonists of the purinergic receptor evoke marked increases in [Ca 2+ ] i in β-cells isolated from transplantable human islets of Langerhans (11) . (springer.com)
  • Addition of pyruvate to rat islets perifused in the presence of 5 mM-glucose elicited an immediate pronounced biphasic stimulation of insulin secretion. (biochemj.org)
  • A marked stimulation of insulin secretion and 45Ca2+ efflux rate was observed in response to 3-fluoropyruvate and 3-bromopyruvate, compounds which inhibited oxidative metabolism of [14C]glucose and [14C]pyruvate in islets. (biochemj.org)
  • Lumelsky N, Blondel O, Laeng P, Velasco I, Ravin R, McKay R (2001) Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. (springer.com)
  • However, the pharmacology of the defined I 1 - and I 2 -imidazoline sites does not correlate with the observed responses to imidazolines in islets, although I 2 -receptors (also known as non-adrenoceptor idazoxan binding sites (NAIBS)) have been described in pancreatic islets 5 and RINm5F insulinoma cells 6 . (springer.com)
  • Enriched islets were cultured to permit adhesion and stimulate islet-derived cell proliferation (emersion phase). (endocrine-abstracts.org)
  • The transplantation of pancreatic islets for the treatment of type I diabetes is hindered by the enormous loss of cells due to early apoptotic events. (elsevier.com)
  • Genetic engineering of islets with cytoprotective genes is an important strategy aimed to enhance the survival of these cells in the transplant setting. (elsevier.com)
  • Alternative sources such as human embryonic stem cell-derived β-cells and porcine islets have the potential to satisfy demand, although efficacy, safety and regulatory issues remain to be addressed. (nature.com)
  • An encapsulation strategy that can prevent the rejection of xenogeneic islets or of stem cell-derived allogeneic islets can potentially eliminate both of these barriers. (nature.com)
  • 12 . A method for stimulating the differentiation of pancreatic cells to islets of Langerhans cells comprising increasing the availability of at least one of the islet cell growth hormones which is centrally and/or peripherally stimulated. (google.com)
  • Researchers craft hormone-producing pancreas cells from human embryonic stem cells, paving the way for a cell therapy to treat diabetes. (the-scientist.com)
  • Beta cells (green) in the pancreas secrete insulin to regulate blood glucose levels WIKIMEDIA, MASUR Scientists claim to have successfully grown insulin-secreting pancreatic beta cells from human embryonic stem cells. (the-scientist.com)
  • The insulin-producing cells in the pancreas play a crucial role in the management of our blood sugar levels. (europa.eu)
  • The number of beta cells in the pancreas increases in response to greater demand for insulin or injury, but it is not clear if the new beta cells are the result of cell division or the differentiation of a precursor cell, a process known as neogenesis. (medicalxpress.com)
  • No evidence for beta cell neogenesis in murine adult pancreas, J Clin Invest. (medicalxpress.com)
  • Scientists generally think that reduced insulin production by the pancreas, a hallmark of type 2 diabetes, is due to the death of the organ's beta cells. (medicalxpress.com)
  • However, those cells come from pancreas tissue provided by organ donors. (vetscite.org)
  • The Salk technology begins with induced pluripotent cells (iPSC), a stem cell technique where tissue from a patient-such as skin-is reprogrammed into other types of cells, such as from the pancreas. (technologynetworks.com)
  • In the mouse the developing pancreas is controlled by contact with, and signalling molecules secreted from, surrounding cells. (biomedsearch.com)
  • The present study was undertaken to determine whether embryonic stem (ES) cells could be used as an alternative model in vitro system to investigate the role of cell-cell interactions in the developing pancreas. (biomedsearch.com)
  • A research team which is experimenting on mice has found a way to convert another type of pancreas cell into the critical insulin-producing beta cells. (medindia.net)
  • They found that treating adult stem cells in the pancreas with a naturally occurring hormone can transform the stem cells into beta cells, which secrete insulin. (stemcellresearch.org)
  • Currently, there are limited ways to preserve or recover insulin secretory capacity in human pancreas. (yonsei.ac.kr)
  • In pre-trial studies, BCG was shown to destroy the blood cells that attack the pancreas and prevent it from making insulin. (diabetestalk.net)
  • Leaders in the field discuss how in vivo cell lineage reprogramming can be used for tissue repair and regeneration in different organs, including brain, spinal cord, pancreas, liver and heart. (springer.com)
  • Type 1 diabetes is an autoimmune disorder in which the immune system attacks and destroys insulin-producing islet cells of the pancreas. (nature.com)
  • While terminally differentiated beta cells are only present in the pancreas, endocrine progenitors with similar features to pancreatic endocrine progenitors are also found in the intestine. (medpagetoday.com)
  • The enteroendocrine system is comprised of many different cell types, some of which are shared in common with the endocrine pancreas (for example, somatostatin- and ghrelin-producing cells), and some of which are organ specific," the researchers wrote. (medpagetoday.com)
  • a benign tumor of the insulin-secreting cells of the pancreas that may produce signs of hypoglycemia. (dictionary.com)
  • Melton is also collaborating with a researcher at the Massachusetts Institute of Technology to surmount the other major challenge in treating type 1 diabetes: stopping the immune system from attacking and killing the beta cells within the pancreas that secrete insulin. (bostonglobe.com)
  • Biologists have found a hormone in the liver that spurs the growth of insulin-secreting cells in the pancreas, a discovery they hope will lead to new treatments for diabetes. (scientificamerican.com)
  • Douglas Melton, a Harvard University stem cell scientist, and colleagues reported the in vitro feat on Thursday (October 9) in Cell . (the-scientist.com)
  • In vitro it has been demonstrated using rodent and clonal insulin-secreting cells that purinergic receptor activation is coupled to an increase in [Ca 2+ ] i (3-6) . (springer.com)
  • In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow," Diabetes , vol. 53, no. 7, pp. 1721-1732, 2004. (hindawi.com)
  • Moritoh Y, Yamato E, Yasui Y, Miyazaki S, Miyazaki J (2003) Analysis of insulin-producing cells during in vitro differentiation from feeder-free embryonic stem cells. (springer.com)
  • By differential-display PCR a subclone of the SKBR3 cell line with high in vitro transendothelial invasiveness was identified to express increased levels of the INSL-4 gene. (aacrjournals.org)
  • PrSC, but not LNCaP and DU-145 cells, secreted significant amounts of IGF-I. Coculture with PrSC increased the growth of DU-145 cells in vitro but the pretreatment of PrSC with small interfering RNA of IGF-I did not enhance it. (aacrjournals.org)
  • Anti-IGF-IR antibodies, IGF-IR inhibitors, and antisense oligonucleotides to IGF-IR successfully suppress prostate cancer cell growth in vitro and in vivo ( 11 - 13 ). (aacrjournals.org)
  • Thus, the stromal cells not only accelerate the growth of tumor cells ( 19 , 20 ) but also suppress it ( 21 , 22 ) in vitro and in vivo . (aacrjournals.org)
  • Recent studies have shown that certain compounds which possess an imidazoline moiety within their structure, are able to enhance the rate of insulin secretion, both in vivo and in vitro 1 . (springer.com)
  • 3) nestin-immunostaining of long-term in vitro grown insulinoma cell suspensions, and (4) phase-contrast light microscopy for analyzing the in vitro growth characteristics of the insulinoma cells. (cu.edu.tr)
  • 4) insulin secretion rates after 6 weeks of in vitro growth ranged from 3.5 to 83.3 mu U/ml/h/60,000 cells plated, and (5) after long-term in vitro growth of insulk noma-derived cell suspensions with persistent insulin-secreting capacity, nestin staining was observed predominantly in co-cultured fibroblasts. (cu.edu.tr)
  • Conclusion: Our data describe for the first time the long-term in vitro culture of insulin-secreting human insulinomas and highlight the importance of beta-cell trophic factors for insulinoma cell growth. (cu.edu.tr)
  • Glycation of insulin in vitro was substantially less extensive than in BRIN-BD11 cells, although glucose-6-phosphate and glyceraldehyde-3-phosphate were 1.4- to 2.0-fold more reactive than glucose per se. (ulster.ac.uk)
  • After differentiating hEAs into insulin-secreting cells (hEA-ISCs) in vitro, cells were transplanted into a type 2 diabetes mouse model. (yonsei.ac.kr)
  • To investigate the differentiation of human amniotic epithelial cells (hAECs) into insulin secreting cells (ISCs) in vitro . (bvsalud.org)
  • Additionally, the data show that despite its weak in vitro inhibition of caspase-3, PI-9 affords significant protection against TNF-α-induced apoptosis in these cells. (elsevier.com)
  • When transplanted into diabetic mice, converted human α-cells reverse diabetes and continue to produce insulin even after six months. (nature.com)
  • The project's team has developed new imaging techniques that allow researchers to find out more about beta cells, the pancreatic cells that produce insulin. (europa.eu)
  • People with T1D are dependent on external insulin therapy to survive, as their bodies do not produce insulin on their own, and they cannot maintain safe blood glucose levels without treatment. (businesswire.com)
  • The researchers showed that the new cells could produce insulin when they encountered sugar. (vetscite.org)
  • In order to produce insulin-secreting cells with a high value of glucose-stimulated insulin secretion (GSIS) from mouse embryonic stem cells, we have developed an optimized 5-stage protocol by referring to culture conditions so far reported elsewhere. (springer.com)
  • Although cells made in a dish were able to produce insulin, they were sluggish or simply unable to respond to glucose. (technologynetworks.com)
  • This step yields the pre-beta cells, which produce insulin but are not yet functional. (technologynetworks.com)
  • Pancreatic beta cells must be able to do two things to work effectively: respond to glucose and produce insulin," says Evans, who is also a Howard Hughes Medical Institute investigator and the March of Dimes Chair in Molecular and Developmental Biology. (technologynetworks.com)
  • I know that when glucose enters a beta cell it triggers the cell to produce insulin. (stackexchange.com)
  • A biological process allows the capsule to continuously produce insulin, rather than using up a limited supply. (nsf.gov)
  • The research, published in Nature Communications, details new cells that produce insulin when they encounter sugar in both culture and mouse trials. (diabetestalk.net)
  • By deleting a single gene in human gut endocrine progenitor and serotonin-producing cells, researchers reported that they were able convert them into cells that produce insulin. (medpagetoday.com)
  • The findings, reported online in Nature Communications , may lead to novel type 1 diabetes treatments that involve coaxing existing gut cells in patients to produce insulin and release it when needed, according to Domenico Accili, MD , of Columbia University Medical Center in New York City, and colleagues. (medpagetoday.com)
  • Consequently, beta-cell insulin resistance can contribute to the development and progression of type 2 diabetes. (medicalxpress.com)
  • UC San Francisco researchers have discovered a new biological pathway in fat cells that could explain why some people with obesity are at high risk for metabolic diseases such as type 2 diabetes. (medicalxpress.com)
  • Since these experiments have proven it's possible to make beta cells from the tissue of patients with type 1 diabetes, it's likely the technique also would work in patients with other forms of the disease - including type 2 diabetes, neonatal diabetes and Wolfram syndrome. (vetscite.org)
  • For more than a decade, scientists across the globe strived to replace failing pancreatic beta cells linked to immune destruction in children (type 1 diabetes) or obesity-associated diabetes in adults (type 2 diabetes). (technologynetworks.com)
  • Risk factors for type 2 diabetes mellitus preceded by β-cell dysfunction, insulin resistance, or both in older adults: the Cardiovascular Health St. (nih.gov)
  • Insulin resistance (IR) and pancreatic β-cell dysfunction lead to type 2 diabetes mellitus (DM). (nih.gov)
  • We evaluated the efficacy of cell therapy using insulin-secreting cells differentiated from human eyelid adipose tissue-derived stem cells (hEAs) into type 2 diabetes mice. (yonsei.ac.kr)
  • Transplantation of hEA-ISCs lowered blood glucose level in type 2 diabetes mice by increasing circulating insulin level, and ameliorating metabolic parameters including IL-6. (yonsei.ac.kr)
  • Type 2 diabetes is characterized by impaired insulin secretion by pancreatic beta cells in response to a rise in blood glucose levels . (phys.org)
  • UC San Diego scientists - led by PDRC director Maike Sander, PhD, professor in the UCSD Departments of Pediatrics and Cellular and Molecular Medicine - studied the molecular mechanisms that underlie loss of beta cell functional properties, such as regulated insulin secretion, during the progression of type 2 diabetes. (phys.org)
  • They concluded that - by impairing beta cell function - reduced Nkx6.1 levels, as seen in type 2 diabetes, could contribute to its pathogenesis. (phys.org)
  • Instead, a sequential loss of beta cell traits preceding the adoption of alternative endocrine cell fates was observed after adult Nkx6.1 inactivation, which closely mirrors the gradual loss of functional beta cell mass previously observed in models of type 2 diabetes. (phys.org)
  • Dysfunction of the pancreatic beta- cell is an important defect in the pathophysiological changes of type 2 diabetes , and type 2 diabetes is evidently associated with obesity . (bvsalud.org)
  • The present results indicate that adipocytes are directly involved in pancreatic beta- cell dysfunction, which may facilitate the development of type 2 diabetes . (bvsalud.org)
  • Defining the key steps that lead to the specificity in insulin signaling presents a major challenge to biochemical research, but the outcome should offer new therapeutic approaches for treatment of patients suffering from insulin-resistant states, including type 2 diabetes. (jci.org)
  • In this article, we review some of our current understanding about early insulin signal transduction through the network of IRS interacting proteins and the mechanisms that may modify insulin signal transduction in insulin-resistant states, especially obesity and type 2 diabetes. (jci.org)
  • Adults with type 2 diabetes mellitus respond to medical treatment by producing more insulin, but there is no long-term effect on insulin secretion after treatment stops, concluded a pair of clinical trials. (news-medical.net)
  • These studies looked at how medical treatment affected insulin-producing beta cell function in obese people with impaired glucose tolerance (prediabetes), or those who were diagnosed with type 2 diabetes within the last year. (news-medical.net)
  • By examining the effects of different treatments in people with prediabetes and early type 2 diabetes, who still produce substantial amounts of insulin, we hope to learn how to reverse or slow the progressive loss of insulin production that comes with increasing duration of the disease, so that these people can stay healthier longer," said scientist Peter Savage. (news-medical.net)
  • Poor beta-cell function is central to the development of prediabetes and type 2 diabetes, and causes glucose to pile up in the blood. (news-medical.net)
  • A decrease in the function of the cells late in life is the main cause of type 2 diabetes, a metabolic disorder that affects more than 300 million people worldwide. (scientificamerican.com)
  • Melton thinks that injections of betatrophin once a month, or perhaps even once a year, could induce enough activity in pancreatic β cells to provide the same level of blood-sugar regulation for people with type 2 diabetes as daily insulin injections do. (scientificamerican.com)
  • Worms with defective daf-2 genes, for example, correspond to insulin resistance and Type 2 diabetes, the disease of people who make insulin but whose bodies do not respond to it correctly. (nytimes.com)
  • These findings indicate that INS-1 cells have remained stable and retain a high degree of differentiation which should make them a suitable model for studying various aspects of beta-cell function. (nih.gov)
  • Then we compared the gender difference of the pancreatic progenitor cells, and also the dosage of pregnant serum on the efficiency of differentiation. (omicsonline.org)
  • Kunisada Y, Tsubooka-Yamazoe N, Shoji M, Hosoya M (2012) Small molecules induce efficient differentiation into insulin-producing cells from human induced pluripotent stem cells. (springer.com)
  • The insulin-like growth factor (IGF) axis is involved in the regulation of cellular proliferation, differentiation, and apoptosis ( 1 , 2 ). (aacrjournals.org)
  • During this period cells proliferated (proliferation phase) and aggregated into islet-like cell clusters (ILCC) (differentiation phase). (endocrine-abstracts.org)
  • At the end of the differentiation phase Ob-ILCC expressed higher levels of insulin and glucagon. (endocrine-abstracts.org)
  • Conclusions: Ob efficiently stimulated islet-derived cell proliferation and precursor cell differentiation into novel insulin and glucagon secreting ILCC. (endocrine-abstracts.org)
  • A factor(s) secreted from MIN-6 beta-cells stimulates differentiation of definitive endoderm enriched embryonic stem cells towards a pancreatic lineage. (biomedsearch.com)
  • Transwell culture experiments showed that MIN-6 beta-cells secreted a factor or factors that promoted differentiation of ES cell derived definitive endoderm enriched cells towards a pancreatic fate. (biomedsearch.com)
  • Collectively, these results suggest that beta-cells secrete a factor(s) capable of controlling their own differentiation and maturation. (biomedsearch.com)
  • These observations suggest that EGF is closely involved in differentiation of PRL-ir cells from GH-ir cells via MS cells in GH3 cell cultures. (elsevier.com)
  • Bieberich, E 2005, ' Replacement of insulin by LongR3-IGF-1 allows for the differentiation of ES cells into neuroprogenitors and insulin-secreting cells ', Analytical Biochemistry , vol. 346, no. 1, pp. 185-187. (elsevier.com)
  • At different times after differentiation, the expression of insulin and beta2 microglobulin (beta2-MG) was determined by immunocytochemical staining , while the content of insulin in supernatant from cultured hAECs was detected by radioimmunoassay and the expressions of insulin , pancreatic and duodenal homeobox factor-1 (PDX-1) mRNA were detected by reverse transcriptase - polymerase chain reaction (RT-PCR). (bvsalud.org)
  • The ability of both rMAPC and HypoSC to differentiate to functional β-cell like cells may serve to gain insight into signals that govern β-cell differentiation and aid in developing culture systems to commit other (pluripotent) stem cells to clinically useful β-cells for cell therapy of T1D. (elsevier.com)
  • Immunohistochemical analyses of multiple differentiation experiments conducted with three separate iPS lines demonstrated the presence of insulin/C-peptide/CGA-positive cells. (medpagetoday.com)
  • The present invention discloses methods for therapeutically treating mammals, including but not limited to humans, to increase the relative insulin producing performance of endogenous pancreatic β-cells, to cause differentiation of pancreatic epithelial cells into insulin producing β-cells, to improve. (google.com)
  • The present invention discloses methods for therapeutically treating mammals, including but not limited to humans, to increase the relative insulin producing performance of endogenous pancreatic β-cells, to cause differentiation of pancreatic epithelial cells into insulin producing β-cells, to improve muscle sensitivity to insulin and other weight control efforts by the chronic oral administration of a DP IV-inhibitor. (google.com)
  • The extended presence of such hormones, in particular in the pancreatic tissue can also facilitate differentiation and regeneration of the β-cells already present that are in need of repair. (google.com)
  • 7 . The method of claim 1 wherein said step of increasing the availability of islet cell growth hormone to pancreatic cells promotes differentiation of said pancreatic cells to specialized cells of the islet of Langerhans. (google.com)
  • 17 . A method for increasing a mammal's β-cells' ability to secrete insulin or differentiation of pancreatic cells to β-cells in a mammal comprising increasing within said mammal the availability of islet cell growth hormones which are responsive to central and/or peripheral stimulation and substantially unresponsive to acute changes in circulating nutrient levels in said mammal. (google.com)
  • In view of the advantages of the bulk production of clonal pancreaticbeta cells, an investigation was made of the growth and insulin secretoryfunctions of an electrofusion-derived cell line (BRIN-BD11) immobilizedon a solid microcarrier, cytodex-1 or a macroporous microcarrier,cultispher-G. For comparison, similar tests were performed usingBRIN-BD11 cells present in single cell suspensions or allowed toform pseudoislets. (portlandpress.com)
  • BRIN-BD11 cells immobilized on cytodex-1 or cultispher-Gout-performed single cell suspensions and pseudoislets in terms ofinsulin-secretory responses to glucose and amino acids. (portlandpress.com)
  • 1. The cyclic nucleotide phosphodiesterases (PDEs) present in an insulin secreting cell line, BRIN - BD11, were characterized using calcium/calmodulin, IGF-1, isoenzyme-selective PDE inhibitors and RT - PCR. (strath.ac.uk)
  • We report here that the cyclic GMP-inhibited cyclic AMP specific phosphodiesterase (PDE3B) is expressed as a membrane-bound protein in clonal insulin-secreting BRIN-BD11 cells. (strath.ac.uk)
  • We also demonstrated that insulin growth factor-1 (IGF-1) activates PDE3B in BRIN-BD11 cells. (strath.ac.uk)
  • Characteristics of cellular insulin glycation were examined in the pancreatic B-cell line, BRIN-BD11. (ulster.ac.uk)
  • Glycated insulin was readily secreted by BRIN-BD11 cells upon active stimulation with glucose and other secretagogues. (ulster.ac.uk)
  • Modulation of insulin-secretory activity of BRIN-BD11 cells by co-culture at high glucose with diazoxide, L-alanine or glibenclamide indicated that long-term stimulation of secretion was associated with a decrease in the extent of insulin glycation. (ulster.ac.uk)
  • Effects of glycated and non-glycated tGLP-1 on insulin secretion were examined using glucose-responsive clonal BRIN-BD11 cells. (ulster.ac.uk)
  • In mice, some glucagon-producing pancreatic α-cells and somatostatin-producing δ-cells become insulin-expressing cells after the ablation of insulin-secreting β-cells, thus promoting diabetes recovery. (nature.com)
  • Fig. 1: Glucagon-expressing α-cells efficiently engage insulin production. (nature.com)
  • Conversion of mature human β-cells into glucagon-producing α-cells. (nature.com)
  • In activin-treated cells, mRNA for pancreatic polypeptide (PP) but not that for either insulin or glucagon was detected by reverse transcription-PCR. (jci.org)
  • Depolarizing concentration of potassium, tolbutamide, carbachol, and glucagon-like peptide-1 stimulated the release of immunoreactive insulin. (jci.org)
  • cells revealed that the insulinotropic hormones glucagon and GLP-1 triggered pronounced oscillations in [cAMP]pm. (dissertations.se)
  • Glucagon-like peptide I increases cytoplasmic calcium in insulin-secreting beta TC3-cells by enhancement of intracellular calcium mobilization. (ox.ac.uk)
  • Glucagon-like peptide-1 (7-36) amide (truncated GLP-1, tGLP-1) is a potent insulin releasing hormone of the enteroinsular axis. (ulster.ac.uk)
  • Alpha cells secrete glucagon. (answers.com)
  • It is noted that in addition to GIP secreting K-cells, the glucagon-like peptide 1 (GLP-1) generating L-cells share/ many similarities to pancreatic p-cells, including the peptidases required for proinsulin processing, hormone storage and a glucose-stimulated hormone secretion mechanism. (conicyt.cl)
  • 1973). Gastrointestinal enteroendocrine K-cells and L-cells release the glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1), respectively. (conicyt.cl)
  • Melton's procedure requires six steps, involving chemicals and growth factors, and takes 40 days to go from either embryonic or adult stem cells to mature pancreatic beta cells. (the-scientist.com)
  • Beattie GM, Lopez AD, Bucay N, Hinton A, Firpo MT, King CC, Hayek A (2005) Activin A maintains pluripotency of human embryonic stem cells in the absence of feeder layers. (springer.com)
  • James D, Levine AJ, Besser D, Hemmati-Brivanlou A (2005) TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells. (springer.com)
  • U.S. Patent No. 7,033,831 ("Islet cells from human embryonic stem cells"), issued on April 25th, claims methods "for obtaining human insulin secreting cells. (blogspot.com)
  • This patent discloses a system "[f]or embryonic stem cell derived islet cells to become a commercially viable proposition, there is a need to develop new procedures that provide for populations of islet cells of high purity," and discloses "a system for efficient production of primate cells that have differentiated from pluripotent cells into cells of the islet cell lineage. (blogspot.com)
  • Alan Trounson, Australian embryonic stem cell expert and a leader in the field worldwide, says that stem cell research (both adult and embryonic) has advanced so rapidly in the past few months that therapeutic cloning is now unnecessary. (stemcellresearch.org)
  • Previously, researchers in Sweden used a gene therapy technique to add a growth gene to embryonic stem cells to get adequate growth in culture. (stemcellresearch.org)
  • According to the authors, however, "HSCs of early embryonic origin, including those derived from differentiated embryonic stem cells, are inefficient in engrafting adult recipients upon transplantation. (stemcellresearch.org)
  • However, such conversion into delta and other types of non-beta cells was not observed when Nkx6.1 was inactivated at the embryonic stage. (phys.org)
  • To generate insulin-secreting cells we used two cell sources: rat multipotent adult progenitor cells (rMAPC) and the highly similar rat extra-embryonic endoderm precursor (rXEN-P) cells isolated under rMAPC conditions from blastocysts (rHypoSC). (elsevier.com)
  • Teratoma formation by human embryonic stem cells: evaluation of essential parameters for future safety studies. (nature.com)
  • Researchers have been able to generate pancreatic insulin-producing cells from embryonic and pluripotent stem cells (iPS) in the lab, but for the most part the cells have proven unresponsive to glucose, which regulates insulin production in the body, Accili explained. (medpagetoday.com)
  • Human embryonic stem cell research has emerged as an important platform for the understanding and treatment of pediatric diseases. (aappublications.org)
  • Despite differences in public opinion on this issue, a large majority of the public supports continued research using embryonic stem cells. (aappublications.org)
  • Given the possible substantial benefit of stem cell research on child health and development, the American Academy of Pediatrics believes that funding and oversight for human embryo and embryonic stem cell research should continue. (aappublications.org)
  • In the past 10 years, significant progress has been made in basic and translational research using human embryonic stem cells (hESCs), with specific implications for pediatric diseases such as hypoxic-ischemic encephalopathy, 1 bone marrow failure syndromes, 2 leukemia, 3 and congenital heart disease. (aappublications.org)
  • 10 Traditionally created embryonic stem cell lines are needed to serve as a comparison with the newly developed lines to establish whether they are indeed equivalent to traditionally developed lines. (aappublications.org)
  • Earlier this year, Egli's laboratory was able to create embryonic stem cells from a person with type 1 diabetes , through a process called somatic cell nuclear transfer. (bostonglobe.com)
  • The researchers were able to make the insulin-secreting cells from embryonic stem cells and from another type of stem cell, which avoids many of the ethical quandaries of stem-cell research because they are created by reprogramming people's skin cells into a stem-cell-like state, rather than requiring the destruction of embryos. (bostonglobe.com)
  • According to findings reported in the scientific journal Cell , JDRF-supported Harvard University researcher Doug Melton , Ph.D., has developed a method for converting human stem cells (both embryonic and non-embryonic types) into insulin-producing beta cells in the lab. (jdrf.org)
  • Pancreatic β cells replicate rapidly during embryonic and neonatal stages in both mice and humans, but their growth falls off dramatically in adults. (scientificamerican.com)
  • Embryonic stem cells can turn into any other sort of cell, so might possibly be persuaded to turn into entire people. (scribd.com)
  • Regardless of that possibility, embryonic stem cells have medical promise, and several firms are currently studying them. (scribd.com)
  • Geron, the most advanced of these firms, has worked out how to persuade embryonic stem cells to turn into seven different types of normal cell line that it hopes can be used to repair damaged tissue. (scribd.com)
  • In case that does not work, though, the discussion has turned to the idea of transplanting adult nuclei into embryonic stem cells as a way of getting round the rejection problem. (scribd.com)
  • Last year President George Bush issued a decree restricting federal funding in America to existing embryonic stem-cell lines. (scribd.com)
  • Predominance of β-cell neogenesis rather than replication in humans with an impaired glucose tolerance and newly diagnosed diabetes. (nature.com)
  • Scientists at Scripps Research Institute used bone marrow stem cells to grow new blood vessels in the eyes of mice, a development researchers say could lead to treatments for some forms of blindness in humans, including diabetic retinopathy and macular degeneration. (stemcellresearch.org)
  • Although encapsulation technology has met several challenges, the convergence of expertise in materials, nanotechnology, stem cell biology and immunology is allowing us to get closer to the goal of encapsulated islet cell therapy for humans. (nature.com)
  • β-cell replication has proved difficult to control in humans. (scientificamerican.com)
  • Millman hopes that these stem cell-derived beta cells could be ready for research in humans within 3 to 5 years. (medicalnewstoday.com)
  • The other source of Dr. Ruvkun's research is a microscopic roundworm called Caenorhabditis elegans, a standard laboratory organism surprisingly similar to humans, at least in terms of its cells' basic housekeeping functions. (nytimes.com)
  • A study publishing June 16 in Cell Reports now describes a new genetic mutation as an additional cause of ataxia in humans and mice. (vetscite.org)
  • 7. These findings, in a clonal insulin secreting cell line, are consistent with an important role for PDE3B in regulating the pool of cyclic AMP relevant to the modulation of glucose-induced insulin secretion. (strath.ac.uk)
  • Using a novel multiwell culture plate system, we examined oscillations in insulin release and the ATP/ADP ratio in the clonal insulin-secreting cell lines HIT T-15 and INS-1. (elsevier.com)
  • Here we show that islet non-β-cells, namely α-cells and pancreatic polypeptide (PPY)-producing γ-cells, obtained from deceased non-diabetic or diabetic human donors, can be lineage-traced and reprogrammed by the transcription factors PDX1 and MAFA to produce and secrete insulin in response to glucose. (nature.com)
  • The scientists tested the cells in culture and in mice, and in both cases found that the cells secreted insulin in response to glucose. (vetscite.org)
  • How does the pancreatic beta-cell know how much insulin to secrete in response to glucose? (stackexchange.com)
  • Insulin is secreted by pancreatic β cells in response to glucose stimulation. (sciencemag.org)
  • This suggests that glucose is still capable of eliciting part of the ionic events at the plasma membrane, which leads to insulin secretion. (nih.gov)
  • When K ATP channels were held open with diazoxide (and the plasma membrane partially depolarized with high extracellular KCl), amino acids still stimulated insulin release. (diabetesjournals.org)
  • As intracellular Ca 2+ rises, the exocytotic machinery is activated, which moves secretory granules containing insulin to the plasma membrane surface. (diabetesjournals.org)
  • To enable measurements of the cAMP concentration beneath the plasma membrane ([cAMP]pm) of individual cells, a translocation biosensor was created based on fluorescent-protein-tagged subunits of protein kinase A (PKA). (dissertations.se)
  • Recordings of single-cell insulin secretion kinetics with a fluorescent biosensor that reports formation of the phospholipid PIP3 in the plasma membrane in response to autocrine insulin receptor activation showed that [cAMP]pm oscillations were paralleled by pulsatile insulin release. (dissertations.se)
  • In the new study, a team led by Zhen Gu from the University of North Carolina, Chapel Hill, and North Carolina State University, Raleigh, started with a large, double-layered vesicle that resembles the outer plasma membrane of a beta cell. (nih.gov)
  • 86 Rb + efflux experiments and electrophysiological studies 2,3 have provided evidence that this response is due to the reduction in potassium flux via ATP-regulated K + channels across the islet B-cell plasma membrane, resulting in membrane depolarization. (springer.com)
  • Ca(2+)-activated K+ channels from the plasma membrane of an insulin-secreting hamster Beta-cell line (HIT T15) were incorporated into planar lipid bilayers. (ox.ac.uk)
  • The current theory is that mitochondrial oxidation of glucose leads to increased ATP levels, which is detected by ATP-sensitive potassium channels at the plasma membrane, which in turn leads to secretion of insulin. (stackexchange.com)
  • cells, cAMP potentiates the secretion of insulin by promoting Ca2+ signals and by amplifying Ca2+-triggered exocytosis. (dissertations.se)
  • Apart from regulating the precise kinetics of insulin exocytosis, temporal encoding of cAMP signals might constitute a basis for differential regulation of downstream cellular targets. (dissertations.se)
  • To identify their functional significance, we have generated transgenic mice expressing REST in beta cells (RIP-REST mice), and previously discovered that REST target genes are essential to insulin exocytosis. (epfl.ch)
  • A role for PLD in regulating glucose homeostasis is emerging as the enzyme has recently been identified in events regulating exocytosis of insulin from pancreatic beta-cells and also in insulin-stimulated glucose uptake through controlling GLUT4 vesicle exocytosis in muscle and adipose tissue. (garvan.org.au)
  • Regulated exocytosis, modelled by insulin secretion stimulated by glucose and other secretagogues from pancreatic islet beta cells is mediated by multiple signaling pathways. (nus.edu.sg)
  • Cells grown on both types ofmicrocarrier showed a significant 1.5-1.8-fold acuteinsulin-secretory response to 16.7 mmol/l glucose. (portlandpress.com)
  • By expressing mutated forms of Rac1 in insulin-secreting INS-1 cells that altered the nature of insulin secretion and morphology, this study demonstrated that Rac1 is involved in glucose and forskolin stimulated insulin secretion, probably at the level of recruitment of secretory granules through actin cytoskeletal reorganization. (nus.edu.sg)
  • Expression of syncollin, a secretory granule associated protein originally expressed in exocrine cells, in insulin-secreting INS-1 cells, indicated that complete, not truncated form syncollin, can be sorted into insulin secretory granules specifically and impair regulated insulin secretion in a Ca2+-independent way. (nus.edu.sg)
  • Here, we report that the NES2Y beta-cells that are transfected with the genes encoding the components of K-ATP channels in beta-cells, sulfonylurea receptor (SUR) 1 and Kir6.2, have operational K-ATP channels and show normal intracellular Ca2+ and secretory responses to glucose. (elsevier.com)
  • In this study, we determined cell growth, insulin content, insulin accumulation and insulin secretory function of a insulin-secreting cell line cultured for 3 days with either GLP-1, GLP-1 plus the DPP IV inhibitor diprotin A (DPA) or stable N-acetyl-GLP-1. (qmu.ac.uk)
  • The results indicate that prevention of DPP IV action is necessary for beneficial effects of GLP-1 on pancreatic beta cells and that prolonged exposure to GLP-1(9-36)amide may be detrimental to insulin secretory function. (qmu.ac.uk)
  • A pH-sensitive green fluorescent protein (EGFP) was targeted to secretory granules in RIN1046-38 insulinoma cells by using a construct in which the EGFP gene was preceded by the nucleotide sequence for human growth hormone. (elsevier.com)
  • Consequently, when analyzed in single cells, fluorescence of the targeted EGFP acts as an indicator of pH within secretory granules. (elsevier.com)
  • Stimulation of insulin release by glucose is widely thought to be coupled to a decrease in the activity of ATP-sensitive K + channels (K ATP channels) that is caused by a decreased concentration of free ADP. (diabetesjournals.org)
  • Withdrawal of pyruvate or halogenated analogues from the perfusate resulted in a secondary stimulation of insulin release, 45Ca2+ efflux and, to some extent, 86Rb+ efflux rates. (biochemj.org)
  • A 1.3-fold,2.2-fold and 1.7-fold stimulation of insulin secretion was observed forglucose, L-alanine and L-arginine respectively in single cellsuspensions. (portlandpress.com)
  • Furthermore, IGF-1-dependent stimulation of p42/p44 MAPK and PDE3B was abolished in serum-deprived cells and this was associated with apoptosis. (strath.ac.uk)
  • In the insulin-secreting beta-cell line beta TC3, stimulation with 11.2 mmol/l glucose caused a rise in the intracellular free Ca2+ concentration ([Ca2+]i) in only 18% of the tested cells. (ox.ac.uk)
  • However, less than ∼4% of total cell EGFP was released after 1.5 h of stimulation. (elsevier.com)
  • In the present study, we demonstrate that not only K-cells, but also L-cells engineered with the human preproinsulin gene are able to synthesize, store and, upon glucose stimulation, release mature insulin. (conicyt.cl)
  • Researchers are already trying to replicate the work and are seeking ways to scale the process using robotics, according to Susan Solomon, chief executive of the New York Stem Cell Foundation, who also spoke to the Washington Post . (the-scientist.com)
  • Controlling diabetes may someday involve mining stem cells from the lining of the uterus, Yale School of Medicine researchers report in a new study published in the journal Molecular Therapy. (medicalxpress.com)
  • WOBURN, Mass.--( BUSINESS WIRE )-- Frequency Therapeutics , a biotechnology company spearheading the movement to harness the regenerative potential of target populations of stem cells inside the body, today announced a grant from JDRF , the leading global organization funding type 1 diabetes (T1D) research. (businesswire.com)
  • The grant, matched by Frequency, will fund research to optimize the company's Progenitor Cell Activation (PCA) Regeneration platform, which will explore a small molecule approach to convert intestinal stem cells into cells capable of insulin secretion for the treatment of T1D. (businesswire.com)
  • The importance of this JDRF grant, especially in the wake of our recent collaboration announcement with the Harvard Stem Cell Institute and the U.S. Army, is that it continues to validate the cutting-edge nature of our PCA Regeneration platform," said David Lucchino, President, Co-founder and CEO of Frequency. (businesswire.com)
  • The grant will fund Frequency's research into its PCA Regeneration platform's ability to stimulate gastrointestinal stem cells to differentiate into insulin-producing beta cells, in an effort to discover and develop new therapies for type 1 diabetes. (businesswire.com)
  • We are encouraged by the promise of a therapy that would convert adult intestinal stem cells into functional insulin-secreting cells using small molecule drugs, which could be a key step in developing successful cell replacement therapies for people with type 1 diabetes," said Esther Latres, Ph.D., JDRF Director, Research. (businesswire.com)
  • The JDRF grant follows Frequency's recently announced research collaboration with the Harvard Stem Cell Institute and the U.S. Army to study Frequency's PCA Regeneration platform in muscle indications. (businesswire.com)
  • Frequency activates 'stemness' through mimicking signals provided by neighboring cells (the stem cell niche) with small molecules, and this proprietary approach is known as the Progenitor Cell Activation (PCA) Regeneration platform. (businesswire.com)
  • To receive news and publication updates for Stem Cells International, enter your email address in the box below. (hindawi.com)
  • Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus," Journal of the American Medical Association , vol. 297, no. 14, pp. 1568-1576, 2007. (hindawi.com)
  • Human adipose-tissue derived mesenchymal stem cells differentiate in to insulin, somatostatin and glucagons expressing cells," Science , vol. 341, pp. 1135-1140, 2006. (hindawi.com)
  • Human adipose tissue is a source of multipotent stem cells," Molecular Biology of the Cell , vol. 13, no. 12, pp. 4279-4295, 2002. (hindawi.com)
  • Human adipose tissue-derived mesenchymal stem cells combined with hematopoietic stem cell transplantation synthesize insulin," Transplantation Proceedings , vol. 40, no. 4, pp. 1135-1139, 2008. (hindawi.com)
  • Signaling a potential new approach to treating diabetes, researchers at Washington University School of Medicine in St. Louis and Harvard University have produced insulin-secreting cells from stem cells derived from patients with type 1 diabetes. (vetscite.org)
  • The new discovery suggests a personalized treatment approach to diabetes may be on the horizon - one that relies on the patients' own stem cells to manufacture new cells that make insulin. (vetscite.org)
  • Millman, whose laboratory is in the Division of Endocrinology, Metabolism and Lipid Research, began his research while working in the laboratory of Douglas A. Melton, PhD, Howard Hughes Medical Institute investigator and a co-director of Harvard's Stem Cell Institute. (vetscite.org)
  • There, Millman had used similar techniques to make beta cells from stem cells derived from people who did not have diabetes. (vetscite.org)
  • Some scientists thought that because the tissue would be coming from diabetes patients, there might be defects to prevent us from helping the stem cells differentiate into beta cells. (vetscite.org)
  • Millman said more research is needed to make sure that the beta cells made from patient-derived stem cells don't cause tumors to develop - a problem that has surfaced in some stem cell research - but there has been no evidence of tumors in the mouse studies, even up to a year after the cells were implanted. (vetscite.org)
  • He said the stem cell-derived beta cells could be ready for human research in three to five years. (vetscite.org)
  • A new study by researchers at Karolinska Institutet shows how an unexpectedly high number of mutations in the stem cells of muscles impair cell regeneration. (technologynetworks.com)
  • Have you or a member of your immediate family benefited from a clinical trial or treatment using adult or cord blood stem cells? (stemcellresearch.org)
  • Because hematopoietic (blood forming) stem cells (HSCs) can restore and maintain blood formation following transplantation into immune deficient hosts, growth of HSCs in culture is important for many clinical applications. (stemcellresearch.org)
  • The researchers have now shown that adding the same growth gene, Lhx2, to adult bone marrow stem cells allows unlimited growth of the cells. (stemcellresearch.org)
  • These adult stem cells efficiently rescued immune-compromised mice and generated all blood cells. (stemcellresearch.org)
  • Researchers in Canada and Japan have shown in animal studies that adult stem cells from bone marrow have a unique immunity tolerance. (stemcellresearch.org)
  • When selected bone marrow stem cells of mice were injected into rats, without immunosuppression, the injected cells survived and thrived without being rejected by the host immune system. (stemcellresearch.org)
  • Scientists at Massachusetts General Hospital have successfully turned adult stem cells into insulin-producing cells that could reverse diabetes. (stemcellresearch.org)
  • This means new beta cells could be made from a patient's own pancreatic stem cells to treat their diabetes. (stemcellresearch.org)
  • Adult bone marrow stem cells injected into the eyes of rats with damaged retinas formed new retinal cells. (stemcellresearch.org)
  • The bone marrow stem cells incorporated and differentiated into retinal neural cells in the injured retina. (stemcellresearch.org)
  • Bone marrow stem cells may be useful in repair of damaged retinal cells. (stemcellresearch.org)
  • The injected adult stem cells homed in on the parts of the eye where they were needed, grew new blood vessels, and prevented blindness in the mice. (stemcellresearch.org)
  • Adult bone marrow stem cells implanted into children with osteogenesis imperfecta, a severe bone and cartilage disease, have stimulated growth of bone in these patients. (stemcellresearch.org)
  • What are stem cells? (bioeden.com)
  • Stem cells are the body's master cells. (bioeden.com)
  • All stem cells are not identical but have widely differing abilities. (bioeden.com)
  • Two common types of stem cells currently being used for human therapy are Mesenchymal stem cell s and Hematopoietic stem cells . (bioeden.com)
  • These two different types of stem cells are found in different places in the body and have completely different therapeutic applications. (bioeden.com)
  • Mesenchymal stem cells (MSC) are a well-characterised population of adult stem cells. (bioeden.com)
  • Unlike other types of adult stem cells, Mesenchymal stem cells from teeth can be obtained and expanded to quantities appropriate for medical use. (bioeden.com)
  • I had heard about stem cell technology and how it could repair damaged hearts. (bioeden.com)
  • The host environment is a crucial factor for considering the transplant of stem cell-derived immature pancreatic cells in patients with type 1 diabetes. (4-diabetes.com)
  • Human induced pluripotent stem cell-derived pancreatic endocrine progenitor cells (EPCs), which contained a high proportion of chromogranin A + NK6 homeobox 1 + cells and very few INS + cells, were used. (4-diabetes.com)
  • These findings provide useful insights into postoperative diabetic care for cell therapy using stem cell-derived pancreatic cells. (4-diabetes.com)
  • The most recent attempt to take down diabetes comes from researchers at Washington University School of Medicine in St. Louis and Harvard University, who have managed to change stem cells derived from diabetes patients into insulin-secreting cells. (diabetestalk.net)
  • Dr. Açelya Yilmazer is as an assistant professor at the Biomedical Engineering Department and the vice director of the Stem Cell Institute of Ankara University. (springer.com)
  • She is a member of the International Society of Stem Cell Research and the Biomaterials and Tissue Engineering Society of Turkey. (springer.com)
  • As a result, the elusive goal of generating fully functional insulin-producing cells to free patients with type 1 diabetes from daily insulin injections may be closer to reality, with no stem cell transplantation involved. (medpagetoday.com)
  • However, "we have tried to make insulin-producing cells from stem cells for a long time, and while there have been several incremental steps forward, I would say we are not much closer today than we were 3 or 4 years ago," Accili told MedPage Today . (medpagetoday.com)
  • From its inception, however, it has raised ethical concerns based not on the use of stem cells themselves but on objections to the source of the cells-specifically, the destruction of preimplantation human embryos. (aappublications.org)
  • 4 Although the fundamental principle of stem cell research remains the same (ie, the development of undifferentiated cells into committed cell lineages for the purpose of tissue renewal and repair), the science has evolved to encompass many new applications, including cell-based therapies 5 and drug screening. (aappublications.org)
  • In these cases, the removal of the cells to form the stem cell line results in the destruction of the embryo. (aappublications.org)
  • There is some recent evidence that hESC lines can be generated from 1 to 2 cells obtained by a biopsy procedure that does not require destruction of the embryo, but this procedure has not obviated the need to continue to derive stem cells in the traditional manner, which results in the destruction of an embryo. (aappublications.org)
  • Moreover, although a single cell biopsy may be performed in IVF cases to test for genetic diseases, it is unclear whether it would be appropriate to transfer to a uterus an embryo that underwent such biopsy for the creation of stem cell lines. (aappublications.org)
  • Research is ongoing to identify novel and more efficient methods of obtaining stem cells from human embryos, and it is anticipated that this area will continue to evolve. (aappublications.org)
  • Harvard researcher Douglas Melton developed a process that starts with stem cells and results in pancreatic cells that secrete insulin. (bostonglobe.com)
  • In a paper published in the journal Cell on Thursday , he reported a step-by-step procedure that starts with stem cells and results in hundreds of millions of the precious pancreatic cells that secrete the hormone insulin, keeping blood sugar levels in balance. (bostonglobe.com)
  • Other attempts to use stem cells for diabetes therapy have been making steady progress. (bostonglobe.com)
  • These pathways are reiteratively used during development and adult life, acting to maintain stem cells and direct tissue repair and regeneration. (keystonesymposia.org)
  • A team led by Douglas Melton, co-director of the Harvard Stem Cell Institute in Cambridge, Massachusetts, identified the hormone, betatrophin, by inducing insulin resistance in mice using a peptide that binds to insulin receptors. (scientificamerican.com)
  • Henrik Semb, managing director of the Danish Stem Cell Center in Copenhagen, says that 'the identification of a factor, betatrophin, that stimulates mouse β-cell replication with remarkable efficiency is a very important discovery, because it provides the starting point for further studies to elucidate the underlying mechanism of β-cell replication. (scientificamerican.com)
  • What are stem cells and why are they important? (medicalnewstoday.com)
  • Stem cell research brings regenerative medicine a step closer, but many of the ideas and concepts remain controversial. (medicalnewstoday.com)
  • So what are stem cells, and why are they so important? (medicalnewstoday.com)
  • Stem cells are a type of cell that can develop into many other types of cell. (medicalnewstoday.com)
  • Stem cells can also renew themselves by dividing, even after they have been inactive for a long time. (medicalnewstoday.com)
  • Instead, it produces stem cells that have a wide range of possible functions. (medicalnewstoday.com)
  • However, stem cells need to become a specific cell type to be useful. (medicalnewstoday.com)
  • When a stem cell divides, the new cells may either become another stem cell or a specific cell, such as a blood cell, a brain cell, or a muscle cell. (medicalnewstoday.com)
  • Scientists call a stem cell an undifferentiated cell because it can become any cell. (medicalnewstoday.com)
  • Stem cells may provide the key to regenerative medicine, in which the body heals itself. (medicalnewstoday.com)
  • In some tissues, stem cells play an essential role in regeneration, as they can divide easily to replace dead cells. (medicalnewstoday.com)
  • Scientists believe that knowing how stem cells work may lead to possible treatments for conditions, such as diabetes and heart disease . (medicalnewstoday.com)
  • For instance, if someone's heart contains damaged tissue, doctors might be able to stimulate healthy tissue to grow by transplanting laboratory-grown stem cells into the person's heart. (medicalnewstoday.com)
  • The results showed a 40 percent reduction of the size of scarred heart tissue caused by heart attacks when doctors transplanted stem cells to the damaged area. (medicalnewstoday.com)
  • This makes it difficult to tell whether the improvement in heart function resulted from the transplantation of stem cells or whether it was due to something else. (medicalnewstoday.com)
  • For example, all of the transplants took place while the individuals were undergoing heart bypass surgery, so it is possible that the improvement in heart function was due to the bypass rather than the stem cell treatment. (medicalnewstoday.com)
  • This study will include a control group of people with heart failure who undergo bypass surgery but who do not receive the stem cell treatment. (medicalnewstoday.com)
  • Another investigation, published in Nature Communications in 2016, has suggested that stem cell therapies could be the basis of personalized diabetes treatment. (medicalnewstoday.com)
  • In mice and laboratory-grown cultures, researchers successfully produced insulin-secreting cells from stem cells derived from the skin of people with type 1 diabetes . (medicalnewstoday.com)
  • Stem cells could have vast potential in developing new therapies. (medicalnewstoday.com)
  • Or instead of putting the nucleus into an egg cell, it might be put into a socalled stem cell from an early embryo. (scribd.com)
  • But some countries are getting nervous about stem-cell research. (scribd.com)
  • This nervousness has not been calmed by the activities of Advanced Cell Technology, a firm based in Worcester, Massachusetts, which announced in November 2001 that it had managed the trick of transplanting adult nuclei into stem cells and persuading the result to divide a few times. (scribd.com)
  • At least 351 companies across the United States are marketing unapproved stem cell procedures at 570 individual clinics. (vetscite.org)
  • Stem cell research brings regenerative medicine a step closer, but there is also controversy. (medicalnewstoday.com)
  • A stem cell is known as an "undifferentiated cell," because it can still become any kind of cell. (medicalnewstoday.com)
  • Stem cells could help the body to heal itself. (medicalnewstoday.com)
  • In some tissues, stem cells play an important role in regeneration, as they can easily divide, and they can keep replacing dead cells. (medicalnewstoday.com)
  • For instance, if someone has damaged tissue in their heart, it might be possible to stimulate the growth of healthy tissue by transplanting laboratory-grown stem cells into the patient's heart. (medicalnewstoday.com)
  • They also reported a 70 percent improvement in quality of life 24 months after being injected with the stem cells. (medicalnewstoday.com)
  • To investigate further, the researchers plan to do another study, this time including a control group of patients with heart failure who undergo bypass surgery, but who do not receive the stem cell treatment. (medicalnewstoday.com)
  • Glucokinase is present in the cytoplasm and a vesicular/granule compartment that is partially colocalized with insulin granules. (diabetesjournals.org)
  • The glucokinase activity associated with the insulin granules may have a role in either direct or indirect coupling between glucose phosphorylation and insulin secretion. (diabetesjournals.org)
  • They packed it full of small vesicles containing the same type of lab-made insulin currently used to treat diabetes, mimicking the insulin-storage granules found inside mature beta cells. (nih.gov)
  • Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells. (nature.com)
  • The data indicate that InsP3 receptors are present in only a small subfraction of the Ca2+ ATPase-containing Ca2+ stores in INS-1 and pancreatic beta-cells, and that cADP ribose/caffeine-sensitive Ca(2+)-induced Ca2+ release channels may be entirely absent from this endocrine cell type. (nih.gov)
  • AR42J cells provide a model system to study the formation of pancreatic endocrine cells. (jci.org)
  • Here, we investigated the effect of insulin (INS)-deficient diabetes on the fate of immature pancreatic endocrine cell grafts and the underlying mechanisms. (4-diabetes.com)
  • Immunohistochemical analyses indicated that the grafts from diabetic mice contained more endocrine cells including proliferative INS-producing cells compared with that from nondiabetic mice, despite no difference in whole graft mass between the two groups. (4-diabetes.com)
  • These data suggest that INS-deficient diabetes upregulates the INS-secreting capacity of EPC grafts by increasing the number of endocrine cells including INS-producing cells without changing the graft mass. (4-diabetes.com)
  • rather they are part of a burgeoning body of evidence indicating that enteric and pancreatic endocrine cells can convert into different subtypes, possibly through a dedifferentiation process," they wrote. (medpagetoday.com)
  • The researchers first used fluorescence immunohistochemistry to survey FOXO1 localization in the human gut, finding that FOXO1 expression defines endocrine progenitor and serotonin-positive cells. (medpagetoday.com)
  • RESEARCH DESIGN AND METHODS: We generated mice harboring a conditional deletion of survivin in pancreatic endocrine cells using mice with a Pax-6-Cre transgene promoter construct driving tissue-specific expression of Cre-recombinase in these cells. (biomedsearch.com)
  • RESULTS: Selective deletion of survivin in pancreatic endocrine cells in the mouse had no discernible effects during embryogenesis but was associated with striking decreases in beta-cell number after birth, leading to hyperglycemia and early-onset diabetes by 4 weeks of age. (biomedsearch.com)
  • Serum insulin levels were significantly decreased in animals lacking endocrine cell survivin, with relative stability of other hormones. (biomedsearch.com)
  • The AβCs are engineered to "sense" a rise in blood glucose, triggering biochemical changes in the vesicle and the automatic release of some of its insulin load until blood glucose levels return to normal. (nih.gov)
  • We present methodologies for assessing cellular PLD activity in secretagogue-stimulated insulin-secreting pancreatic beta-cells and also insulin-stimulated adipocyte and muscle cells, two of the principal insulin-responsive cell types controlling blood glucose levels. (garvan.org.au)
  • In young people, beta cells respond more sensitively to increases in blood glucose levels, but their function also declines more rapidly and irreversibly in this group. (news-medical.net)
  • Over time, the insulin deficit, and therefore the average blood glucose levels, increases in both categories. (news-medical.net)
  • While on treatment, adult patients showed better beta cell function in terms of weight loss and stable blood glucose levels. (news-medical.net)
  • New imaging techniques developed through EU support are enabling researchers to take a closer look at the birth, life and death of these precious cells in their quest to improve the prevention and management of diabetes. (europa.eu)
  • The researchers behind the new study have previously shown that the insulin-secreting beta-cell, situated in the pancreatic islet of Langerhans, not only produces the hormone insulin but is also a target for insulin signaling . (medicalxpress.com)
  • More than two decades ago, Washington University researchers Paul E. Lacy, MD, PhD, now deceased, and David W. Scharp, MD, began transplanting such cells into patients with type 1 diabetes. (vetscite.org)
  • First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. (biologists.org)
  • To find out, the researchers injected artificial cells suspended in a water-based gel under the skin of diabetic mice that don't make insulin. (nih.gov)
  • The Salk researchers found that, indeed, when the matured beta cells were transplanted into type 1 diabetic mice, the procedure quickly rescued their diabetes. (technologynetworks.com)
  • Researchers have nailed down yet another component of the mechanotransduction complex responsible for relaying signals from hair cells in the ear. (the-scientist.com)
  • A team of researchers have been trying to figure it out, because persuading adipocytes to produce MORE adiponectin, could be rather helpful, in someone who is insulin resistant. (betterbodychemistry.com)
  • Writing about their findings in the journal Cell, the researchers have revealed that the secret ingredient is a single transcription factor. (medindia.net)
  • The researchers say that the body then senses a loss of alpha cells, replaces them with new alpha cells, and then converts those too into beta cells. (medindia.net)
  • Previous studies done by researchers have identified insulin as an important new weapon for fighting infection and healing wounds. (medindia.net)
  • According to researchers, a low dose of oral interferon alpha shows promise in preserving beta cell function for patients with newly diagnosed type 1 diabetes, or juvenile diabetes. (medindia.net)
  • Researchers at the Pediatric Diabetes Research Center (PDRC) at the University of California, San Diego School of Medicine have shown that the pancreatic protein Nkx6.1 - a beta-cell enriched transcription factor - is essential to maintaining the functional state of beta cells. (phys.org)
  • The deletion resulted in the expansion of the enteroendocrine Neurogenin3 (Neurog1)-positive progenitor cell pool, and the appearance of functional insulin-producing cells that expressed all markers of mature pancreatic beta cells, secreted insulin in response to physiologic and pharmacologic cues, and readily regenerated, the researchers reported. (medpagetoday.com)
  • To determine whether human enteroendocrine cells could be manipulated to yield insulin-producing cells, the researchers transduced 170-day-old organoids with adenovirus expressing the dominant-negative mutant FOXO1 HA-delta-256 and analyzed them for 2 weeks. (medpagetoday.com)
  • When the researchers used lentivirus encoding FOXO1 small hairpin RNA (shRNA) as an alternative approach to inhibit FOXO1 function, they found that transduction of 230-day-old organoids with the virus decreased FOXO1 mRNA significantly, accompanied by the appearance of insulin-immunoreactive cells. (medpagetoday.com)
  • Further experiments showed that 8-week-old mice injected with betatrophin showed an average 17-fold rise in the replication of their insulin-secreting pancreatic β cells, the researchers report in Cell . (scientificamerican.com)
  • Suppression of epithelial-to-mesenchymal transitioning enhances ex vivo reprogramming of human exocrine pancreatic tissue toward functional insulin-producing β-like cells. (nature.com)
  • Non-invasive cell type selective in vivo monitoring of insulin resistance dynamics, Scientific Reports (2016). (medicalxpress.com)
  • Decreased levels of Cdk5r2 in beta cells of RIP-REST mice further confirmed that it is controlled by REST, in vivo. (epfl.ch)
  • Examples from various animal models are given and the regenerative potential of in vivo reprogramming is compared to that of cell transplantation studies. (springer.com)
  • The cells release C-peptide in response to secretagogues and survive in vivo following transplantation into mice. (medpagetoday.com)
  • Then transplantation was conducted in pre-diabetes model mice, in which GSIS was impaired without affecting insulin producing function. (springer.com)
  • The transplantation of 5 × 10 6 cells resulted in a marked improvement of glucose tolerance within 20 days. (springer.com)
  • We thank Dr. Niwa for the donation of feeder free EB3 cells, and Dr. Okitsu for excellent technical support on transplantation. (springer.com)
  • Cell Transplantation , 13 (5), 489-496. (elsevier.com)
  • The autoimmune response in type 1 diabetes combined with the response to allogeneic cell transplantation remains a formidable barrier to transplant success that currently requires the use of powerful immunosuppressive drugs. (nature.com)
  • Encapsulation strategies have the potential to ameliorate these responses to promote survival post-transplantation, with modifications to the biomaterial chemistry, the incorporation of biologics or cell co-transplantation being used to avoid lifelong immunosuppression. (nature.com)
  • Vascularization of the transplant site is being developed to enhance islet function post-transplantation by providing the nutrients necessary for survival, while also allowing the sensing of glucose and the distribution of insulin. (nature.com)
  • Figure 1: Islet and β-cell transplantation systems. (nature.com)
  • We conclude that amino acid-induced insulin release depends on two components: a yet-unknown amino acid sensor and K ATP channels, which serve to attenuate hormone release when cellular energy stores are low. (diabetesjournals.org)
  • Pancreatic beta cells store and release insulin, the hormone responsible for stimulating cells to convert glucose to energy. (medicalxpress.com)
  • The action of the hyperglycemia-inducing hormone galanin, a 29-amino acid peptide named from its N-terminal glycine and C-terminal amidated alanine, was studied in rat insulinoma (RINm5F) cells using electrophysiological and 86Rb+ flux techniques. (pnas.org)
  • In conclusion, the pancreatic progenitor cells could be differentiated to insulin-secreting islet β-cells by the pregnant serum, which indicates the therapeutic potential of hormone therapy in preventing and/or treating diabetes. (omicsonline.org)
  • Pituitary tumor GH3 cells synthesize and secrete both growth hormone (GH) and prolactin (PRL). (elsevier.com)
  • Patients with Type 1 diabetes lack the ability to create their own insulin, meaning they rely on regular injections of the hormone to control blood sugar. (diabetestalk.net)
  • Insulin is an anabolic hormone with powerful metabolic effects. (jci.org)
  • Insulin is a hormone that helps the body take glucose from the bloodstream into its cells, for use as fuel in multiple cellular processes. (news-medical.net)
  • 1 . A method for improving β-cell capacity to secrete insulin in response to increased glucose levels comprising increasing the availability of islet cell growth hormone to pancreatic cells wherein said islet cell growth hormone circulates at a level which is substantially unresponsive to acute changes in glucose level. (google.com)
  • 2 . The method of claim 1 wherein said increasing step comprises potentiating the activity of said islet cell growth hormone. (google.com)
  • 3 . The method of claim 2 wherein said islet cell growth hormone is PACAP. (google.com)
  • Frequency's precise and controlled approach transiently causes Lgr5+ progenitor cells to divide and differentiate, much like what is seen in naturally regenerating tissues such as the skin and intestine. (businesswire.com)
  • To fuel its drug discovery programs, Frequency is leveraging a PCA screening platform using primary human cells, including cochlear progenitor cells and adult human progenitor cells from the GI tract. (businesswire.com)
  • Here, we reported that under the stimuli of hormones, pancreatic duct epithelial cells, also known as pancreatic progenitor cells, could be differentiated into insulin-secreting islet β-cells. (omicsonline.org)
  • After 7 days of culturing, the pancreatic progenitor cells will be aggregated. (omicsonline.org)
  • A possible event is ghrelin/Ob-induced regeneration of damaged β-cell population through the recruitment of pancreatic progenitor cells (PPC). (endocrine-abstracts.org)
  • And beta cells do a much better job controlling blood sugar than diabetic patients can. (vetscite.org)
  • In diabetic RIP-REST mice, high levels of REST were associated with postnatal beta cell apoptosis, which resulted in gradual beta cell loss and sustained hyperglycemia in adults. (epfl.ch)
  • Salk scientists have solved a longstanding problem in the effort to create replacement cells for diabetic patients. (technologynetworks.com)
  • When we added ERR-gamma to pre-diabetic beta cells in a dish, we successfully created a glucose-responsive, beta-like cell," says Eiji Yoshihara, first author of the paper and a Salk research associate. (technologynetworks.com)
  • Given that levels of Nkx6.1 are also reduced in human type 2 diabetic beta cells, our study lends support to the growing concept that loss of beta cell features could contribute to the onset of diabetes," Sander said. (phys.org)
  • β-cell replacement may efficiently cure type 1 diabetic (T1D) patients whose insulin-secreting β-cells have been selectively destroyed by autoantigen-reactive T cells. (elsevier.com)
  • 2000). When rendered diabetic by streptozotozin-mediated destruction of their pancreatic p -cells, these animals showed normal glucose tolerance tests results and expressed human insulin in cells in the stomach and duodenum. (conicyt.cl)
  • We used clonal βHC9 cells, which derive from hyperplastic islet cells of transgenic mice that express the SV40 T-antigen under the control of an insulin promoter ( 10 ). (diabetesjournals.org)
  • In this issue of the Journal of Clinical Investigation , George Gittes and colleagues at the Children's Hospital of Pittsburgh used a fluorescent cell labeling method in mice to determine exactly when precursor cells develop into pancreatic beta cells . (medicalxpress.com)
  • These data demonstrate that beta cell neogenesis is not possible in adult mice. (medicalxpress.com)
  • The produced cells were transplanted in diabetes model mice but no remedy effect was observed. (springer.com)
  • Introduction: The ghrelin gene products ghrelin and obestatin (Ob) protect mice from STZ-induced β-cell death, inflammation and STZ-induced diabetes. (endocrine-abstracts.org)
  • The result is the production of hundreds of millions of lab-produced human beta cells-able to relieve diabetes in mice. (technologynetworks.com)
  • In mice, adult cone cell outer segments and their visual functions deteriorate if two microRNAs are not present. (the-scientist.com)
  • Some experts believe that even if the findings in mice translate to human tissue, scientists would need to find a way to turn Pax4 on and then back off again once a sufficient number of beta cells are in place. (medindia.net)
  • Serum levels of glucose, insulin and c-peptide were measured, and changes of metabolism and inflammation were assessed in mice that received undifferentiated hEAs (UDC group), differentiated hEA-ISCs (DC group), or sham operation (sham group). (yonsei.ac.kr)
  • Significantly increased levels of human insulin and c-peptide were detected in sera of DC mice. (yonsei.ac.kr)
  • RT-PCR and immunohistochemical analysis showed human gene expression and the presence of human cells in kidneys of DC mice. (yonsei.ac.kr)
  • The study, published in the September 26 edition of Cell Reports , shows that loss of NKx6.1 in mice caused rapid onset diabetes. (phys.org)
  • Inactivating the Nkx6.1 transcription factor in adult mice , then conducting a genome-wide analysis of Nkx6.1-regulated genes and functional assays, the scientists revealed the critical role of this protein in the control of insulin biosynthesis, insulin secretion and beta cell proliferation . (phys.org)
  • Transgenic mice carrying the human insulin gene driven by the K-cell glucose-dependent insulinotropic peptide (GIP) promoter secrete insulin and display normal glucose tolerance tests after their pancreatic p-cells have been destroyed. (conicyt.cl)
  • The IGF axis consists of two major ligands (IGF-I and IGF-II), two cell-surface receptors (IGF-IR and IGF-IIR), six binding proteins (IGFBP-1 to 6) that regulate IGF availability to the receptors, and a group of IGFBP proteases that cleave IGFBP and modulate the action of IGFs ( 2 , 3 ). (aacrjournals.org)
  • This results in activation of the receptor kinase and tyrosine phosphorylation of a family of insulin receptor substrate (IRS) proteins. (jci.org)
  • The phosphorylated insulin receptor binds and phosphorylates IRS proteins and Shc, which bind differentially to various downstream signaling proteins. (jci.org)
  • PH domains, which are found in most of the proteins that interact with the insulin receptor, bind to charged headgroups of specific phosphatidylinositides and are thereby targeted preferentially to membrane structures. (jci.org)
  • The membrane acts as a 'microfilter,' allowing the secretion of insulin from the capsule but blocking the entrance of antibodies. (nsf.gov)
  • An alternative mechanism of activation by pyruvate and its halogenated derivatives is proposed, based on the possible electrogenic flux of these anions across the cell membrane. (biochemj.org)
  • The glucose-induced [cAMP]pm oscillations are generated by periodic cAMP production mediated by interplay between ATP and Ca2+ in the sub-membrane space, and may contribute to both triggering and amplifying pathways of insulin secretion. (dissertations.se)
  • Rac1, a member of Rho GTPase, primarily regulates the formation of lamellipodial and ruffles by reorganization of cell membrane cortex filamentous actins. (nus.edu.sg)
  • At a membrane potential of + 20 mV, which is close to the peak of the Beta-cell action potential, channel activity was half-maximal at a Ca2+ concentration of about 15 mumol/l. (ox.ac.uk)
  • A silicon membrane containing nano-scale pores allows the insulin out and keeps out antibodies secreted by the immune system. (nsf.gov)
  • 4. The results suggest that sparteine and amantadine can block the K-ATP channel from either side of the membrane and support the idea that at least part of the stimulatory effect of these agents on insulin secretion results from inhibition of this channel. (ox.ac.uk)
  • Trypsin activated channels only when applied to the intracellular surface of the cell membrane. (dundee.ac.uk)
  • When an action potential depolarizes the cell membrane, voltage-gated Ca2+ channels (e.g. (wikipedia.org)
  • Marian Blanca Ramírez from the CSIC in Spain has been studying the effects of LRRK2, a protein associated with Parkinson's disease, on cell motility. (biologists.org)
  • Gu and his colleagues started by borrowing GLUT2, the major glucose transporting protein from a real beta cell, and anchoring the protein to the outer surface of the AβCs. (nih.gov)
  • This protein switch, called ERR-gamma, turned out to be crucial to awaken silent beta-like cells that could now respond to glucose and release insulin accordingly. (technologynetworks.com)
  • Further studies using MIN-6 condition medium showed that the factor(s) involved was restricted to MIN-6 cells, could be concentrated with ammonium sulphate, and was sensitive to heat treatment, suggesting that it was a protein or peptide. (biomedsearch.com)
  • Cellular insulin glycation was decreased by 66-80% by inhibitors of protein glycation, vitamin C, aminoguanidine or acetylsalicylic acid. (ulster.ac.uk)
  • Cells were transduced using a Maloney murine leukemia virus (MLV) vector coding for yellow fluorescent protein (YFP) and for one of the following antiapoptotic genes: cFLIP, FADD-DN, BcL-2, PI-9, and ICAM-2. (elsevier.com)
  • Like other growth factors, insulin uses phosphorylation and the resultant protein-protein interactions as essential tools to transmit and compartmentalize its signal. (jci.org)
  • PI3-kinase is critical for metabolic actions of insulin, such as glucose transport, glycogen synthesis, and protein synthesis, whereas Grb-2/SOS complex, which activates the MAP kinase cascade, is critical in mitogenic response. (jci.org)
  • Some of the best-characterized protein interaction domains involved in insulin signaling are the PH (pleckstrin homology), PTB (phosphotyrosine binding), SH2, and SH3 domains ( 1 ) (Table 1 ). (jci.org)
  • The protein encoded by this gene is a regulator of the pancreatic beta-cell function. (wikipedia.org)
  • This protein has been shown to prevent MAPK8 mediated activation of transcription factors, and decrease IL-1 beta and MAP kinase kinase 1 (MEKK1) induced apoptosis in pancreatic beta cells. (wikipedia.org)
  • After reading the "instructions" in its DNA, the cell will produce protein molecules that can take sugar from the environment, break it down, and rebuild it into the drugs -- in the same general way that yeast usually breaks sugar down and turns it into alcohol. (washingtonpost.com)
  • The gene, known to worm experts as daf-2 (for dauer formation), directs the cell to produce a receptor protein that straddles the cell wall. (nytimes.com)
  • It is also not necessarily clear if a specific case is caused by loss of function or by insulin resistance, as diabetes is usually diagnosed using tests that cannot distinguish between the two. (europa.eu)
  • The new method, presented in the journal Scientific Reports , can be used to assess insulin resistance during progression and intervention of metabolic diseases. (medicalxpress.com)
  • Insulin resistance is a key contributing factor to a variety of metabolic diseases , including cardio-vascular disease, the metabolic syndrome and diabetes type 2. (medicalxpress.com)
  • This technique allows monitoring of cell type specific insulin sensitivity or resistance in real-time in the context of whole body insulin resistance during progression and intervention of disease", says Professor Per-Olof Berggren, who led the current study together with Associate Professor Ingo Leibiger at the Rolf Luft Research Center for Diabetes and Endocrinology. (medicalxpress.com)
  • Whilst insulin supplements can be used to maintain blood glucose, insulin-resistance is increasing among diabetes patients. (technologynetworks.com)
  • In fact, TOO MUCH INSULIN, causes cells to stop listening to insulin - this situation is described as INSULIN RESISTANCE. (betterbodychemistry.com)
  • And these shortages are linked with insulin resistance. (betterbodychemistry.com)
  • In the longitudinal analysis, measures of homeostatic model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-B) in 1992-1993 were used as additional criteria to subclassify incident DM into its subtypes (preceded predominantly by IR, β-cell dysfunction, or both). (nih.gov)
  • Associations of major diabetes risk factors with insulin resistance (IR) and β-cell dysfunction, Cardiovascular Health Study, 1989-1992. (nih.gov)
  • Notably, insulin-producing α-cells maintain expression of α-cell markers, as seen by deep transcriptomic and proteomic characterization. (nature.com)
  • Ectopic PDX-1 expression directly reprograms human keratinocytes along pancreatic insulin-producing cells fate. (nature.com)
  • Chera, S. & Herrera, P. L. Regeneration of pancreatic insulin-producing cells by in situ adaptive cell conversion. (nature.com)
  • Solid tumors are composed of tumor cells and surrounding stroma including extracellular matrix, fibroblasts, macrophages, and endothelial cells ( 15 , 16 ). (aacrjournals.org)
  • The growth of tumor cells as well as that of normal epithelial cells is regulated by the stromal cells through diffusible factors and their adhesion ( 17 , 18 ). (aacrjournals.org)
  • Cellular blebs shed by tumor cells can process short stretches of RNA that go on to induce tumor formation in neighboring cells. (the-scientist.com)
  • These cells can make insulin but they don't release it when they are supposed to," he said. (medpagetoday.com)
  • In theory, if we could replace the damaged cells in these individuals with new pancreatic beta cells - whose primary function is to store and release insulin to control blood glucose - patients with type 1 diabetes wouldn't need insulin shots anymore," said first author Jeffrey R. Millman, PhD, an assistant professor of medicine and of biomedical engineering at Washington University School of Medicine. (vetscite.org)
  • We found the loss of Nkx6.1 activity had an immediate and dramatic impact on the expression of genes that give beta cells their ability to synthesize and release insulin in a regulated fashion," said Sander. (phys.org)
  • In theory, if we could replace the damaged cells in these individuals with new pancreatic beta cells - whose primary function is to store and release insulin to control blood glucose - patients with type 1 diabetes wouldn't need insulin shots anymore. (medicalnewstoday.com)
  • Establishing the existence of other types of cells that can process and secrete transgenic insulin would help the development of new gene therapy strategies to treat patients with diabetes mellitus. (conicyt.cl)
  • Thus, besides pancreatic p-cells, both gastrointestinal enteroendocrine K-cells and L-cells can be selected as the target cell in a gene therapy strategy to treat patients with type 1 diabetes mellitus. (conicyt.cl)
  • 2004). Thus, it is expected that if gastrointestinal enteroendocrine cells of patients with type 1 diabetes mellitus were endowed with the ability to express the preproinsulin gene, they could contribute to the normalization of postprandrial blood glucose. (conicyt.cl)
  • Cell Calcium. (nih.gov)
  • Calcium currents in insulin-secreting beta-cells. (ox.ac.uk)
  • rMAPCr/HypoSC progeny secreted C-peptide under the stimulus of insulin agonist carbachol, and was inhibited by the L-type voltage-dependent calcium channel blocker nifedipine. (elsevier.com)
  • Fura-2 was used to reflect changes in intracellular calcium concentration ([Ca(2+)](i)) in MIN6 cells . (bvsalud.org)
  • As we have previously shown, a synthetic ligand of PPARalpha, fenofibrate, has a stimulatory effect on insulin secretion in clonal hamster insulinoma beta-cell line HIT-T15 cells. (ox.ac.uk)
  • 6. IBMX, Org 9935, siguazodan and rolipram (1 - 50 microM), but not zaprinast, each augmented glucose-induced insulin secretion in the presence of 16.7 mM but not 1 mM glucose. (strath.ac.uk)
  • Stimulatory levels of glucose doubled EGFP secretion from cell cultures, and potentiators of glucose-induced insulin secretion enhanced EGFP release. (elsevier.com)
  • People with this form of diabetes can't make their own insulin and require regular insulin injections to control their blood sugar. (vetscite.org)
  • It is treated with insulin injections. (medindia.net)
  • Ultimately, the hope is those cells could be transplanted into diabetes patients and allow them to create insulin naturally, creating a paradigm shift in treating a disease currently kept in check by insulin injections. (bostonglobe.com)
  • Fig. 2: Insulin-producing human α-cells reverse mouse diabetes. (nature.com)
  • Fig. 3: Transcriptomic and proteomic analyses of insulin-producing human α-cells. (nature.com)
  • Fig. 4: scRNA-seq analysis of insulin-producing human α-cells. (nature.com)
  • Fig. 5: Immunogenicity tests on insulin-producing human α-cells. (nature.com)
  • Human pancreatic beta-like cells converted from fibroblasts. (nature.com)
  • Epigenomic plasticity enables human pancreatic α to β cell reprogramming. (nature.com)
  • This could also help us to overcome several current obstacles in beta cell replacement, including the scarcity of functional human beta cells. (businesswire.com)
  • However, few studies have examined intracellular Ca 2+ signalling in isolated human insulin-secreting cells (4,7-10) . (springer.com)
  • In this paper we examine: (i) the purinergic receptor subtype present in human tissue, (ii) compare purinergic receptor-evoked increases in [Ca 2+ ] i in both rodent and human β-cells and (iii) demonstrate that intracellular Ca 2+ signals can also be recorded in cryopreserved human β-cells originally isolated from cadaver organ donors. (springer.com)
  • With further study, the findings suggest that AβCs might be implanted directly into human skin via an injectable gel and without the immunosuppressive drugs required for the transfer of live cells. (nih.gov)
  • Using our coculture system, we have found that PrSC increased the growth of human prostate cancer LNCaP and DU-145 cells ( 25 ). (aacrjournals.org)
  • Disruptions in β-cell function and glucose homeostasis are well-established physiologic hallmarks of human diabetes. (technologynetworks.com)
  • We found the missing energy switch needed to produce robust and functional human beta cells, potentially turning this discovery into a viable treatment for human diabetes," says Ronald Evans, co-senior author and director of the Gene Expression Laboratory at Salk. (technologynetworks.com)
  • No one had been able to figure out how to make pancreatic cells from human patients that can do both until now. (technologynetworks.com)
  • He adds that the team's technique is an easy, fast and inexpensive way to make transplantable human pancreatic beta cells in a dish that genetically match patients. (technologynetworks.com)
  • thereby obtaining a population comprising human insulin secreting cells. (blogspot.com)
  • NES2Y is a proliferating human insulin-secreting cell line that we have derived from a patient with persistent hyperinsulinemic hypoglycemia of infancy. (elsevier.com)
  • Single-cell genome analyses reveal the amount of mutations a human brain cell will collect from its fetal beginnings until death. (the-scientist.com)
  • Browse other questions tagged human-biology cell-biology metabolism endocrinology or ask your own question . (stackexchange.com)
  • The hAECs were isolated from human amnion by trypsin digestion , and the phenotype of the isolated cells were identified by flow cytometry and immunocytochemical staining . (bvsalud.org)
  • Hydrochlorothiazide: An hyperglycaemia-inducing agent and K-ATP channel agonist in human beta-cells and clonal insulin-secreting cells. (elsevier.com)
  • Nucleotide sequencing of cDNAs encoding human insulin-like growth factor I (IGF-I) predicts the existence of two different prohormone forms of IGF-I. The E peptide regions extend the carboxy-terminus of the 70 amino acid core IGF-I molecule (BCAD domains) by either an additional 35 (IGF-Ia) or 77 (IGF-Ib) amino acids. (elsevier.com)
  • Employing antiserum directed against a peptide sequence unique to the E peptide region of IGF-Ia prohormone, we have identified EIa immunoreactive material (IR-EIa) in the conditioned medium of a human hepatoma cell line, HepG2. (elsevier.com)
  • Inhibition of transcription factor FOXO1 promotes generation of human GI cells into insulin-positive cells that express all markers of mature pancreatic B cells. (medpagetoday.com)
  • Their new research demonstrated that human cells respond in the same way as the mouse cells. (medpagetoday.com)
  • When the mouse enteroendocrine STC-1 cell line was transfected with the human preproinsulin gene, driven either by the K-cell specific GIP promoter or by the constitutive cytomegalovirus (CMV) promoter, human insulin co-localizes in vesicles that contain GIP (GIP or CMV promoter) or GLP-1 (CMV promoter). (conicyt.cl)
  • Dr. Melton's new method of driving the full conversion is an important advance towards potential large-scale, rapid production of human beta cells. (jdrf.org)
  • Currently, sources of human beta cells are largely limited to cadaver donors. (jdrf.org)
  • JDRF is thrilled with this advancement toward large scale production of mature, functional human beta cells by Dr. Melton and his team," said JDRF Chief Scientific Officer Richard A. Insel, MD. "This significant accomplishment has the potential to serve as a cell source for islet replacement in people with T1D when used in encapsulated cell-replacement products. (jdrf.org)
  • JDRF recently awarded a new multi-million dollar research grant to Dr. Melton, for scaling up production of beta cells using his new method, to hopefully provide a virtually unlimited supply of human beta cells. (jdrf.org)
  • The human body requires many different types of cell to function, but it does not produce each cell type fully formed and ready to use. (medicalnewstoday.com)
  • When Dr. Ruvkun ran the daf-2 gene through the gene bank at the National Library of Medicine, he scored a hit on a most surprising target -- the human gene that makes the receptor for insulin. (nytimes.com)
  • Young women who received the human papillomavirus (HPV) vaccine through a school-based program had fewer cervical cell anomalies when screened for cervical cancer, found a new study in CMAJ (Canadian Medical Association Journal). (vetscite.org)
  • 86Rb+ efflux from insulinoma cells is stimulated by galanin in a dose-dependent manner. (pnas.org)
  • 1. Alloxan and its auto-oxidation product hydrogen peroxide (H2O2) irreversibly depolarize insulinoma cells by opening a non-selective cation channel. (dundee.ac.uk)
  • A physiological mixture of amino acids greatly stimulated insulin release at 0-30 mmol/l glucose but affected the concentration of free ADP only to a minor degree and significantly so only at ≤2 mmol/l glucose. (diabetesjournals.org)
  • A Travelling Fellowship from Journal of Cell Science allowed her to spend time in Prof Maddy Parson's lab at King's College London, learning new cell migration assays and analysing fibroblasts cultured from individuals with Parkinson's. (biologists.org)
  • We investigated the subcellular localization, mobility, and activity of glucokinase in MIN6 cells, a glucose-responsive insulin-secreting beta-cell line. (diabetesjournals.org)
  • Breast cancer cell line SKBR3 was obtained from the American Type Culture Collection (Rockville, MD) and cultured in DMEM (ICN, Eschwege, Germany) supplemented with 2 m m l -glutamine, antibiotic drugs as described below, and 10% FCS. (aacrjournals.org)
  • Ca(2+)-activated K+ channels from an insulin-secreting cell line incorporated into planar lipid bilayers. (ox.ac.uk)
  • Amantadine and sparteine inhibit ATP-regulated K-currents in the insulin-secreting beta-cell line, HIT-T15. (ox.ac.uk)
  • 1. The effects of pharmacological agents that potentiate insulin release were studied on ATP-regulated K-currents (K-ATP currents) in the insulin-secreting beta-cell line HIT-T15 by use of patch-clamp methods. (ox.ac.uk)
  • Effect of peroxisome proliferator-activated receptor alpha ligand fenofibrate on K(v) channels in the insulin-secreting cell line HIT-T15. (ox.ac.uk)
  • Fura-2 fluorescence was used to investigate the effects of H2O2 on [Ca2+](i) in the insulin-secreting cell line CRI-G1. (elsevier.com)
  • The present study was designed to evaluate and compare the effects of five genes on a cell line derived from insulin-producing β-cells, NIT-1. (elsevier.com)
  • The effects of the proteolytic enzyme trypsin upon ATP-sensitive potassium (KATP) channel activity were examined in the CRI-G1 insulin-secreting cell line. (dundee.ac.uk)
  • We essentially put DNA into the yeast cells that give it the instructions to build a chemical assembly line process that ends with the medicines we want," Smolke said. (washingtonpost.com)
  • American Journal of Physiology - Cell Physiology , 283 (2 52-2), C429-C437. (elsevier.com)
  • This effect of glucose was counteracted by competitive inhibitors of glucokinase (5-thioglucose and mannoheptulose) but was unaffected by fructose analogs and may be due to changes in cell shape or conformation of the cytoskeleton that are secondary to glucose metabolism. (diabetesjournals.org)
  • It is proposed that oxidative metabolism of pyruvate is not a prerequisite for its stimulatory actions on pancreatic beta-cells. (biochemj.org)
  • Dr Jarrod Marto's lab from the Dana-Farber Cancer Institute recently published a paper in Nature Metabolism on a multi-omic approach used to characterize primary insulin-secreting pancreatic β-cells using the timsTOF Pro - details of which are described in this app note. (technologynetworks.com)
  • The new work was published in Cell Metabolism on April 12, 2016. (technologynetworks.com)
  • You are correct that phosphorylation and further metabolism of glucose by the beta cells is required for sensing. (stackexchange.com)
  • When glucose levels fall, beta cells reduce their glucose metabolism because they use the glucokinase enzyme to phosphorylate glucose, and glucokinase is a low-affinity enzyme that becomes inactive at lower glucose levels. (stackexchange.com)
  • Their findings demonstrate an intricate link between the beta cell's ability to import glucose, supporting an emerging concept that glucose metabolism plays a critical role in beta cell proliferation. (phys.org)
  • They discovered that genes involved in insulin biosynthesis, glucose import and glucose metabolism are direct transcriptional target genes of Nkx6.1. (phys.org)
  • Insulin secretion from glucose-stimulated pancreatic β-cells is oscillatory, and this is thought to result from oscillations in glucose metabolism. (elsevier.com)
  • He has found two families of genes that are involved in relaying messages about sugar metabolism to the information center in the nucleus of living cells. (nytimes.com)
  • The finding implied that the worm makes insulin, too, a fact unknown hitherto, and that it uses insulin to control both its fat metabolism and its hibernation program. (nytimes.com)
  • The product of daf-16 operates in the nucleus of the cell and exerts a negative influence: it switches off the genes responsible for glucose metabolism. (nytimes.com)
  • The absence of the transcriptional repressor RE-1 Silencing Transcription Factor (REST) in insulin-secreting beta cells is a major cue for the specific expression of a large number of genes. (epfl.ch)
  • These REST target genes were largely ascribed to a function of neurotransmission in a neuronal context, whereas their role in pancreatic beta cells has been poorly explored. (epfl.ch)
  • Screening for REST target genes identified several anti-apoptotic genes bearing the binding motif RE-1 that were downregulated upon REST expression in INS-1E cells, including Gjd2, Mapk8ip1, Irs2, Ptprn, and Cdk5r2. (epfl.ch)
  • Together, these data document that a set of REST target genes, including Cdk5r2, is important for beta cell survival. (epfl.ch)
  • Its ablation also indirectly impacted the expression of numerous genes important for the function and proliferation of beta cells. (phys.org)
  • These genes were able to protect NIT-1 cells from cytokine-induced apoptosis to varying degrees ranging from no protection to significant protection equivalent to an optimal dose of a chemical caspase inhibitor. (elsevier.com)
  • First, they carefully tracked the formation of beta cells during development, looking at which genes turned on and off. (bostonglobe.com)
  • That would mean reactivating a whole lot of genes that skin cells don't need but eggs do. (scribd.com)
  • 60% of the thapsigargin-sensitive Ca2+ pool in RINm5F cells. (nih.gov)
  • ATP elicited similar increases in intracellular Ca2+ concentration ([Ca2+]i) in single, living INS-1 and RINm5F cells, and similar fold increases in InsP3 levels in cell populations. (nih.gov)
  • The Ca2+ ATPase inhibitor thapsigargin, added after ATP, caused smaller [Ca2+]i increases in RINm5F than in INS-1 cells. (nih.gov)
  • In partial support of the above hypothesis, patients with a mutant glucokinase of abnormal affinity to glucose have an abnormal set point for glucose homeostasis ( 3 , 4 , 5 ), and other patients with K ATP channels with abnormally low affinity for ADP fail to turn off insulin release properly at low concentrations of blood glucose ( 6 , 7 ). (diabetesjournals.org)
  • As glucose levels return to normal outside the cell, glucose concentrations inside the vesicle also drop, raising the pH. (nih.gov)
  • When glucose concentrations returned to normal levels, the release tailed off to just minimal amounts of insulin. (nih.gov)
  • They respond to high glucose concentrations by secreting insulin, and stop (or reduce) secreting insulin when glucose concentration falls. (stackexchange.com)
  • incubation of HepG2 cells with GH at maximal concentrations (1-5 μg/ml) increased specific IR-EIa in 24 h conditioned medium 3-fold. (elsevier.com)
  • Prostate cancer shows high expression of type I insulin-like growth factor (IGF-I) receptor (IGF-IR) and prostate stromal cells (PrSC) produce IGF-I. Although high plasma level of IGF-I is a risk factor of prostate cancer, the significance of the prostate stromal IGF-I in the regulation of prostate cancer remains elusive. (aacrjournals.org)
  • The events after insulin binds to its receptor are highly regulated and specific. (jci.org)
  • The insulin receptor belongs to the large family of growth factor receptors with intrinsic tyrosine kinase activity. (jci.org)
  • Following insulin binding, the receptor undergoes autophosphorylation on multiple tyrosine residues. (jci.org)
  • This lack or loss of beta cell function is a main cause of diabetes. (europa.eu)
  • "Losing beta cells is something that happens in every patient in the long run, " says Prof. Martin Gotthardt of Radboud University Medical Centre in the Netherlands, BetaImage's project coordinator. (europa.eu)
  • A safe, non-invasive way to check the state of patients' beta cells could help to make treatments more effective, and the BetaImage team was determined to provide it. (europa.eu)
  • As one of several promising outcomes, the team has identified targets specific to these beta cells and developed radioactive tracer molecules that bind to them, making the cells visible for imaging equipment that detects this radiation. (europa.eu)
  • He adds that the initial results are encouraging and that the possibilities extend well beyond establishing beta cell mass. (europa.eu)
  • Different tracers can potentially be used to assess different aspects - for example, if the beta cells are active, or if they are under attack from the immune system. (europa.eu)
  • These cells proliferated slowly (population doubling time about 100 h) and, in general, showed morphological characteristics typical of native beta-cells. (nih.gov)
  • The content of immunoreactive insulin was about 8 micrograms/10(6) cells, corresponding to 20% of the native beta-cell content. (nih.gov)
  • INS-1 cells retain beta-cell surface antigens, as revealed by reactivity with the antigangloside monoclonal antibodies R2D6 and A2B5. (nih.gov)
  • The affinity of beta-cells for glucose is slightly lower than that in cell extracts and, unlike that in hepatocytes, is unaffected by fructose, tagatose, or a high-K+ medium, which is consistent with the lack of change in glucokinase distribution or release. (diabetesjournals.org)
  • Knowledge of how beta cells are created and maintained is critical to understanding diseases in which these cells are lost, such as diabetes. (medicalxpress.com)
  • Simply put, people develop diabetes because they don't have enough pancreatic beta cells to produce the insulin necessary to regulate their blood sugar levels. (medicalxpress.com)
  • In type 1 diabetes (T1D), pancreatic beta cells die from a misguided autoimmune attack, but how and why that happens is still unclear. (medicalxpress.com)
  • This research agreement aims to achieve one of JDRF's key therapeutic goals, exploring beta cell replacement in an effort to achieve insulin independence in people with T1D. (businesswire.com)
  • Thus, a primary and fundamental effective therapy for diabetes is to develop ways to increase beta cell numbers. (omicsonline.org)
  • In these new experiments, the beta cells came from tissue taken from the skin of diabetes patients. (vetscite.org)
  • At that time, Millman expects the cells would be implanted under the skin of diabetes patients in a minimally invasive surgical procedure that would allow the beta cells access to a patient's blood supply. (vetscite.org)
  • The idea of replacing beta cells isn't new. (vetscite.org)
  • Still today, patients in several clinical trials have been given beta cell transplants with some success. (vetscite.org)
  • As with all types of organ donation, the need for islet beta cells for people with type 1 diabetes greatly exceeds their availability. (vetscite.org)
  • Then it would be possible to test the effects of diabetes drugs on the beta cells of patients with various forms of the disease. (vetscite.org)
  • These data indicate the utility ofmicro-carriers for the production of functioning clonal beta cells. (portlandpress.com)
  • Artificial beta cell, made of a lipid bubble (purple) carrying smaller, insulin-filled vesicles (green). (nih.gov)
  • Some of the most exciting possibilities aim to replace the function of the insulin-secreting pancreatic beta cells that is deficient in diabetes. (nih.gov)
  • The latest strategy of this kind is called AβCs, short for artificial beta cells. (nih.gov)
  • The next challenge was to get the AβCs to work like real beta cells, and that took a great deal of time and ingenuity to add the right cellular parts to do the job. (nih.gov)
  • 1] Synthetic beta cells for fusion-mediated dynamic insulin secretion . (nih.gov)
  • Using siRNA-mediated knockdown in INS-1E cells, we showed that Cdk5r2 protects beta cells against cytokines and palmitate-induced apoptosis. (epfl.ch)
  • The Salk team closely studied the basic biology of a beta cell and uncovered several molecular switches, called transcription factors, that were switched off but might control the transition to a fully functional state. (technologynetworks.com)
  • Previously there was nothing known about the maturation process in beta cells. (technologynetworks.com)
  • And when we remove ERR-gamma from animals, the glucose response is eliminated, proving that the factor is the master regulator of maturation for the beta cell. (technologynetworks.com)
  • But can these beta cells successfully treat diabetes? (technologynetworks.com)
  • These results resemble those found for Ca(2+)-activated K+ channels in native Beta cell membranes and indicate that the channel properties are not significantly altered by incorporation in a planar lipid bilayer. (ox.ac.uk)
  • This disease is characterized by unregulated insulin release despite profound hypoglycemia, NES2Y cells, like beta-cells isolated from the patient of origin, lack functional ATP-sensitive potassium channels (K-ATP) and also carry a defect in the insulin gene-regulatory transcription factor PDX1. (elsevier.com)
  • However, these cells, designated NESK beta-cells, have impaired insulin gene transcription responses to glucose. (elsevier.com)
  • NES2Y beta-cells that are transfected with either Kir6.2 or SUR1 alone do not express functional K-ATP channels and have impaired intracellular free Ca2+ concentration-signaling responses to depolarization-dependent beta-cell agonists. (elsevier.com)
  • These findings document that in NES2Y beta-cells, coexpression of both subunits is critically required for fully operational K-ATP channels and K-ATP channel-dependent signaling events. (elsevier.com)
  • How do $\ce\beta$-cells know how much glucose is in the blood? (stackexchange.com)
  • ce\beta$-cells trap glucose by converting it into glucose-6-phosphate , this means $\ce\beta$-cells actually consumes glucose. (stackexchange.com)
  • So my question is: how do $\ce\beta$-cells decide when to stop producing insulin? (stackexchange.com)
  • Yes, pancreatic beta cells can indeed sense the level of blood glucose. (stackexchange.com)
  • Beta cells are the ones lost in type I diabetes patients. (medindia.net)
  • They have found that when the gene called Pax4 is forced on in pancreatic alpha cells, the cells change their identity to become beta cells. (medindia.net)
  • However, Mansouri admits that further studies are needed to show that the alpha to beta cell conversion can be kept under control. (medindia.net)
  • Too many beta cells isn't good either. (medindia.net)
  • Over time, a subset of Nkx6.1-deficient beta cells acquired the molecular characteristics of somatostatin-producing delta cells, suggesting a link between impaired beta cell function and loss of cell identity. (phys.org)
  • But the role of the adipocyte in the dysfunction of the pancreatic beta- cell remains unknown. (bvsalud.org)
  • RE1-silencing transcription factor (REST) is reported to repress the expression of this gene in insulin-secreting beta cells. (wikipedia.org)
  • As blood glucose rises, following a meal, for instance, insulin is produced by specialized cells called beta-cells. (news-medical.net)
  • In prediabetes, some beta cells function, secreting insulin. (news-medical.net)
  • The lack of stable improvement in beta cell function after the withdrawal of medication means that patients with prediabetes or early diabetes must continue to take treatment lifelong. (news-medical.net)
  • The RISE Pediatric Medication Study in 2018 compared treatment with the glargine-metformin sequence, vs metformin alone, in younger patients, but found that beta cells continued to fail while treatment was continuing, with disease progression worsening once medication was stopped. (news-medical.net)
  • It is the lack of insulin produced by those cells, called beta cells, that lies at the root of type 1 diabetes. (bostonglobe.com)
  • He now plans to use Melton's procedure to create the beta cells that are affected by the disease. (bostonglobe.com)
  • Egli said that while he hopes the work will allow him to transplant cells into patients one day, the ability to generate large numbers of beta cells in the laboratory will also aid in the near-term search for diabetes drugs that work on beta cells in diseased patients. (bostonglobe.com)
  • The key, Melton said, is that they were able to make the cells in the quantities that would be needed to treat patients - a coffee cup's worth of beta cells. (bostonglobe.com)
  • Insulin therapy has long been the only method of treating type 1 diabetes (T1D), but a major breakthrough in producing replacement beta cells is bringing new hope that more effective, alternative treatments may be possible. (jdrf.org)
  • After reaching a certain point, the immature cells could only mature into fully functioning beta cells after implantation into animals, and the final conversion took months to occur. (jdrf.org)
  • It may also provide a resource for discovery of therapies that promote survival or regeneration of beta cells and development of screening biomarkers to monitor beta cell health and survival. (jdrf.org)
  • Dr. Melton will also begin working with other members of the JDRF Encapsulation Consortium to conduct animal tests of experimental encapsulation products using this new source of beta cells. (jdrf.org)
  • Can a Spoonful of Sugar Help the Beta Cells Hang 'Round? (jdrf.org)
  • Postnatal expansion of the pancreatic beta-cell mass is dependent on survivin. (biomedsearch.com)
  • OBJECTIVE: Diabetes results from a deficiency of functional beta-cells due to both an increase in beta-cell death and an inhibition of beta-cell replication. (biomedsearch.com)
  • The objective of this study was to determine whether a gene critical for cell division and cell survival in cancer cells, survivin, might also be important for beta-cells. (biomedsearch.com)
  • Exogenous expression of survivin in mature beta-cells lacking endogenous survivin completely rescued the hyperglycemic phenotype and the decrease in beta-cell mass, confirming the specificity of the survivin effect in these cells. (biomedsearch.com)
  • CONCLUSIONS: Our findings implicate survivin in the maintenance of beta-cell mass through both replication and antiapoptotic mechanisms. (biomedsearch.com)
  • It is now obvious that CICR is a widely occurring cellular signaling process present even in many non-muscle cells, such as in the insulin-secreting pancreatic beta cells, epithelium, and many other cells. (wikipedia.org)
  • Prostate cancer cells respond to mitogenic actions of IGF-I ( 5 , 6 ) and prostate cancer tissues show high expression of IGF-IR ( 7 , 8 ). (aacrjournals.org)
  • Download this app note to learn more about high-throughput single-cell RNA sequencing and how it can be used to analyze cells and tissues in a variety of ways. (technologynetworks.com)
  • Zinc is an essential component of the diet and plays a role if a vast array of functions in cells and tissues. (ncl.ac.uk)
  • Immunohistochemistry on tissue microarrays revealed a heterogeneous expression of EPIL in breast cancer tissue and no expression in the surrounding stroma cells. (aacrjournals.org)
  • Finally, by using tissue array immunohistochemistry, we found that, in contrast to the IGF-I and -II expression pattern, EPIL peptides are produced by invasive breast cancer cells. (aacrjournals.org)
  • Cell and Tissue Research , 299 (2), 237-243. (elsevier.com)