Insulin: 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).Islets of Langerhans: 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.Diabetes Mellitus, Type 2: 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.Diabetes Mellitus, Type 1: 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.Diabetes Mellitus: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.Glucose: 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-Secreting Cells: A type of pancreatic cell representing about 50-80% of the islet cells. Beta cells secrete INSULIN.Receptor, Insulin: 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.Insulin Resistance: 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.Blood Glucose: Glucose in blood.Glucose Tolerance Test: 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).Hypoglycemic Agents: Substances which lower blood glucose levels.Diabetes Mellitus, Experimental: Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY.C-Peptide: 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.Diabetes Complications: Conditions or pathological processes associated with the disease of diabetes mellitus. Due to the impaired control of BLOOD GLUCOSE level in diabetic patients, pathological processes develop in numerous tissues and organs including the EYE, the KIDNEY, the BLOOD VESSELS, and the NERVE TISSUE.Glucagon: 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)Hyperglycemia: Abnormally high BLOOD GLUCOSE level.Insulinoma: A benign tumor of the PANCREATIC BETA CELLS. Insulinoma secretes excess INSULIN resulting in HYPOGLYCEMIA.Glucagon-Like Peptide 1: 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.Glucose Clamp Technique: 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.Proinsulin: 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.Insulin Receptor Substrate Proteins: 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.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.Pancreas: 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.Hyperinsulinism: 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.Insulin Antagonists: Compounds which inhibit or antagonize the biosynthesis or action of insulin.Fasting: Abstaining from all food.Hemoglobin A, Glycosylated: 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.Tolbutamide: A sulphonylurea hypoglycemic agent with actions and uses similar to those of CHLORPROPAMIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290)Obesity: 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).Diabetes, Gestational: 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.Insulin, Long-Acting: Insulin formulations that contain substances that retard absorption thus extending the time period of action.Secretory Rate: 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.Cells, Cultured: 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.Insulin Antibodies: Antibodies specific to INSULIN.Hypoglycemia: 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.Diazoxide: A benzothiadiazine derivative that is a peripheral vasodilator used for hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide group.Glucose Transporter Type 2: 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.Calcium: 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.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Gastric Inhibitory Polypeptide: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Sulfonylurea CompoundsFatty Acids, Nonesterified: FATTY ACIDS found in the plasma that are complexed with SERUM ALBUMIN for transport. These fatty acids are not in glycerol ester form.Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.Glucokinase: 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 2.7.1.2.Insulin Infusion Systems: 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.Adipose Tissue: 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.Signal Transduction: 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.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Receptors, Glucagon: 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.Insulin Lispro: 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.Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Prediabetic State: 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).Incretins: Peptides which stimulate INSULIN release from the PANCREATIC BETA CELLS following oral nutrient ingestion, or postprandially.Streptozocin: An antibiotic that is produced by Stretomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals.Postprandial Period: The time frame after a meal or FOOD INTAKE.Rats, Sprague-Dawley: 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.Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.RNA, Messenger: 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.Mice, Knockout: 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.Risk Factors: 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.Sulfonylurea Receptors: ATP-BINDING CASSETTE PROTEINS that are highly conserved and widely expressed in nature. They form an integral part of the ATP-sensitive potassium channel complex which has two intracellular nucleotide folds that bind to sulfonylureas and their analogs.Somatostatin: 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.Venoms: 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.Secretory Vesicles: Vesicles derived from the GOLGI APPARATUS containing material to be released at the cell surface.TriglyceridesKinetics: The rate dynamics in chemical or physical systems.Reference Values: 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.Mice, Inbred C57BLMetformin: 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)Insulin Aspart: Insulin that has been modified to contain an ASPARTIC ACID instead of a PROLINE at position 38 of the B-chain.Body Mass Index: 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)Potassium Channels, Inwardly Rectifying: Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.Insulin, Isophane: 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.Bodily Secretions: Endogenous substances produced through the activity of intact cells of glands, tissues, or organs.Leptin: 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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Adenosine Triphosphate: 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.Glucagon-Secreting Cells: A type of pancreatic cell representing about 5-20% of the islet cells. Alpha cells secrete GLUCAGON.Gene Expression Regulation: 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.Muscle, Skeletal: 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.Mice, Obese: 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.Diabetes Insipidus: A disease that is characterized by frequent urination, excretion of large amounts of dilute URINE, and excessive THIRST. Etiologies of diabetes insipidus include deficiency of antidiuretic hormone (also known as ADH or VASOPRESSIN) secreted by the NEUROHYPOPHYSIS, impaired KIDNEY response to ADH, and impaired hypothalamic regulation of thirst.Cyclic AMP: 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.Models, Biological: 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.KATP Channels: Heteromultimers of Kir6 channels (the pore portion) and sulfonylurea receptor (the regulatory portion) which affect function of the HEART; PANCREATIC BETA CELLS; and KIDNEY COLLECTING DUCTS. KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate.Mannoheptulose: A 7-carbon keto sugar having the mannose configuration.Rats, Inbred Strains: 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.Insulin, Regular, Pork: Regular insulin preparations that contain the SUS SCROFA insulin peptide sequence.Lipids: 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)Adipocytes: 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.Arginine: An essential amino acid that is physiologically active in the L-form.Stimulation, Chemical: 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.Receptors, Drug: Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.Insulins: 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.Islets of Langerhans Transplantation: The transference of pancreatic islets within an individual, between individuals of the same species, or between individuals of different species.Secretory Pathway: A series of sequential intracellular steps involved in the transport of proteins (such as hormones and enzymes) from the site of synthesis to outside the cell. The pathway involves membrane-bound compartments through which the newly synthesized proteins undergo POST-TRANSLATIONAL MODIFICATIONS, packaging, storage, or transportation to the PLASMA MEMBRANE for secretion.Perfusion: Treatment process involving the injection of fluid into an organ or tissue.Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.Eating: The consumption of edible substances.Rats, Zucker: 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.Thiazolidinediones: 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).Lipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.Dietary Fats: 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.Receptor-Like Protein Tyrosine Phosphatases, Class 8: A subclass of receptor-like protein tryosine phosphatases that contain an extracellular RDGS-adhesion recognition motif and a single cytosolic protein tyrosine phosphate domain.Potassium Chloride: A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA.Insulin, Regular, Human: Regular insulin preparations that contain the HUMAN insulin peptide sequence.Adiponectin: 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.Protein PrecursorsMolecular Sequence Data: 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.Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Intestinal Secretions: Fluids originating from the epithelial lining of the intestines, adjoining exocrine glands and from organs such as the liver, which empty into the cavity of the intestines.Bacterial Secretion Systems: In GRAM NEGATIVE BACTERIA, multiprotein complexes that function to translocate pathogen protein effector molecules across the bacterial cell envelope, often directly into the host. These effectors are involved in producing surface structures for adhesion, bacterial motility, manipulation of host functions, modulation of host defense responses, and other functions involved in facilitating survival of the pathogen. Several of the systems have homologous components functioning similarly in GRAM POSITIVE BACTERIA.Congenital Hyperinsulinism: A familial, nontransient HYPOGLYCEMIA with defects in negative feedback of GLUCOSE-regulated INSULIN release. Clinical phenotypes include HYPOGLYCEMIA; HYPERINSULINEMIA; SEIZURES; COMA; and often large BIRTH WEIGHT. Several sub-types exist with the most common, type 1, associated with mutations on an ATP-BINDING CASSETTE TRANSPORTERS (subfamily C, member 8).Glucose Transporter Type 4: 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.Pregnancy in Diabetics: The state of PREGNANCY in women with DIABETES MELLITUS. This does not include either symptomatic diabetes or GLUCOSE INTOLERANCE induced by pregnancy (DIABETES, GESTATIONAL) which resolves at the end of pregnancy.Diabetic Ketoacidosis: 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.Monosaccharide Transport Proteins: A large group of membrane transport proteins that shuttle MONOSACCHARIDES across CELL MEMBRANES.Reverse Transcriptase Polymerase Chain Reaction: 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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Palmitates: Salts and esters of the 16-carbon saturated monocarboxylic acid--palmitic acid.Glucagon-Like Peptides: Peptides derived from proglucagon which is also the precursor of pancreatic GLUCAGON. Despite expression of proglucagon in multiple tissues, the major production site of glucagon-like peptides (GLPs) is the INTESTINAL L CELLS. GLPs include glucagon-like peptide 1, glucagon-like peptide 2, and the various truncated forms.Blotting, Western: 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.Mice, Inbred NOD: A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.PhosphoproteinsPotassium Channels: Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.Insulin-Like Growth Factor I: 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.Biological Transport: 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.GlyceraldehydeDiabetic Nephropathies: KIDNEY injuries associated with diabetes mellitus and affecting KIDNEY GLOMERULUS; ARTERIOLES; KIDNEY TUBULES; and the interstitium. Clinical signs include persistent PROTEINURIA, from microalbuminuria progressing to ALBUMINURIA of greater than 300 mg/24 h, leading to reduced GLOMERULAR FILTRATION RATE and END-STAGE RENAL DISEASE.Carbachol: A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.Blood Glucose Self-Monitoring: 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.Transcription Factor 7-Like 2 Protein: A transcription factor that takes part in WNT signaling pathway. The activity of the protein is regulated via its interaction with BETA CATENIN. Transcription factor 7-like 2 protein plays an important role in the embryogenesis of the PANCREAS and ISLET CELLS.Growth Hormone: 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.Leucine: An essential branched-chain amino acid important for hemoglobin formation.1-Methyl-3-isobutylxanthine: A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASESCell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Disease Models, Animal: 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.Gliclazide: An oral sulfonylurea hypoglycemic agent which stimulates insulin secretion.Metabolic Syndrome X: 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)Palmitic Acid: A common saturated fatty acid found in fats and waxes including olive oil, palm oil, and body lipids.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Fatty Acids: 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)Dietary Carbohydrates: 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)Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.Keto AcidsDeoxyglucose: 2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity.Biological Markers: 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.Phosphatidylinositol 3-Kinases: 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.Dipeptidyl-Peptidase IV Inhibitors: Compounds that suppress the degradation of INCRETINS by blocking the action of DIPEPTIDYL-PEPTIDASE IV. This helps to correct the defective INSULIN and GLUCAGON secretion characteristic of TYPE 2 DIABETES MELLITUS by stimulating insulin secretion and suppressing glucagon release.Insulin, Short-Acting: Insulin derivatives and preparations that are designed to induce a rapid HYPOGLYCEMIC EFFECT.Amino Acid Sequence: 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.Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)Proteins: 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.Diabetic Retinopathy: Disease of the RETINA as a complication of DIABETES MELLITUS. It is characterized by the progressive microvascular complications, such as ANEURYSM, interretinal EDEMA, and intraocular PATHOLOGIC NEOVASCULARIZATION.Enzyme Activation: 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.Colforsin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with LONGITUDINAL STUDIES which are followed over a period of time.Transfection: 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.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Diet, High-Fat: Consumption of excessive DIETARY FATS.Proto-Oncogene Proteins c-akt: 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.Glutamate Decarboxylase: A pyridoxal-phosphate protein that catalyzes the alpha-decarboxylation of L-glutamic acid to form gamma-aminobutyric acid and carbon dioxide. The enzyme is found in bacteria and in invertebrate and vertebrate nervous systems. It is the rate-limiting enzyme in determining GAMMA-AMINOBUTYRIC ACID levels in normal nervous tissues. The brain enzyme also acts on L-cysteate, L-cysteine sulfinate, and L-aspartate. EC 4.1.1.15.Mitochondrial Proteins: Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Energy Metabolism: The chemical reactions involved in the production and utilization of various forms of energy in cells.Body Composition: The relative amounts of various components in the body, such as percentage of body fat.ATP-Binding Cassette Transporters: A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.Cardiovascular Diseases: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.Lipolysis: 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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Diabetic Diet: A diet prescribed in the treatment of diabetes mellitus, usually limited in the amount of sugar or readily available carbohydrate. (Dorland, 27th ed)Pyruvic Acid: An intermediate compound in the metabolism of carbohydrates, proteins, and fats. In thiamine deficiency, its oxidation is retarded and it accumulates in the tissues, especially in nervous structures. (From Stedman, 26th ed)Radioimmunoassay: 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.Diabetic Neuropathies: Peripheral, autonomic, and cranial nerve disorders that are associated with DIABETES MELLITUS. These conditions usually result from diabetic microvascular injury involving small blood vessels that supply nerves (VASA NERVORUM). Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy (see OCULOMOTOR NERVE DISEASES); MONONEUROPATHY; mononeuropathy multiplex; diabetic amyotrophy; a painful POLYNEUROPATHY; autonomic neuropathy; and thoracoabdominal neuropathy. (From Adams et al., Principles of Neurology, 6th ed, p1325)GlycogenEnteroendocrine Cells: Cells found throughout the lining of the GASTROINTESTINAL TRACT that contain and secrete regulatory PEPTIDE HORMONES and/or BIOGENIC AMINES.Islet Amyloid Polypeptide: A pancreatic beta-cell hormone that is co-secreted with INSULIN. It displays an anorectic effect on nutrient metabolism by inhibiting gastric acid secretion, gastric emptying and postprandial GLUCAGON secretion. Islet amyloid polypeptide can fold into AMYLOID FIBRILS that have been found as a major constituent of pancreatic AMYLOID DEPOSITS.Diet: Regular course of eating and drinking adopted by a person or animal.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Ghrelin: 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.Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Hormones: 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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from INCIDENCE, which refers to the number of new cases in the population at a given time.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Hypertension: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Tissue Culture Techniques: A technique for maintaining or growing TISSUE in vitro, usually by DIFFUSION, perifusion, or PERFUSION. The tissue is cultured directly after removal from the host without being dispersed for cell culture.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Oxidation-Reduction: 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).
"Sulfonylurea stimulation of insulin secretion". Diabetes. 51 (Suppl 3): S368-76. doi:10.2337/diabetes.51.2007.S368. PMID ... They are antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release ... While historically people with hyperglycemia and low blood insulin levels were diagnosed with Type I Diabetes by default, it ... Like insulin, sulfonylureas can induce weight gain, mainly as a result of their effect to increase insulin levels and thus ...
The person who was deserving of the 1923 prize for the discovery of insulin as a central hormone for controlling diabetes ( ... Banting FG, Best CH (1922). "The internal secretion of pancreas" (PDF). Journal of Laboratory and Clinical Medicine. 7: 251-266 ... Pavel, I. (1976). "The Priority of N.C. Paulescu in the Discovery of Insulin" [Prioritatea lui N.C. Paulescu în descoperirea ... Murray, Ian (1971). "Paulesco and the Isolation of Insulin". Journal of the History of Medicine and Allied Sciences. 26 (2): ...
Thorens B (Dec 1995). "Glucagon-like peptide-1 and control of insulin secretion". Diabète & Métabolisme. 21 (5): 311-8. PMID ... While it is weak inhibitor of gastric acid secretion, its main role is to stimulate insulin secretion. GIP, along with glucagon ... It is now believed that the function of GIP is to induce insulin secretion, which is stimulated primarily by hyperosmolarity of ... It has been found that Type 2 diabetics are not responsive to GIP and have lower levels of GIP secretion after a meal when ...
Patients with diabetes mellitus might need less insulin or oral antidiabetics when treated with octreotide. The bioavailability ... Mechanism of action is the suppression of insulin secretion. Octreotide can reduce the intestinal resorption of ciclosporin, ... "Caucasian patients having insulin secretion greater than the median of the cohort." "There were no statistically significant ... insulin, secretin, pancreatic polypeptide, TSH, and vasoactive intestinal peptide, reduce secretion of fluids by the intestine ...
In rat pancreas U-II inhibits insulin secretion. It also affects the kidneys including sodium transport, lipid and glucose ... Zhu F, Ji L, Luo B (Nov 2002). "[The role of urotensin II gene in the genetic susceptibility to type 2 diabetes in Chinese ... Its has been linked to cardiac fibrosis and hypertrophy, heart failure, renal dysfunction, and diabetes. GRCh38: Ensembl ... "Role of urotensin II gene in genetic susceptibility to Type 2 diabetes mellitus in Japanese subjects". Diabetologia. 46 (7): ...
"GAD treatment and insulin secretion in recent-onset type 1 diabetes". The New England Journal of Medicine. 359 (18): 1909-20. ... Diabetes[edit]. Both GAD67 and GAD65 are targets of autoantibodies in people who later develop type 1 diabetes mellitus or ... injections with GAD65 have been shown to preserve some insulin production for 30 months in humans with type 1 diabetes.[21][22] ... "Autoimmunity to two forms of glutamate decarboxylase in insulin-dependent diabetes mellitus". The Journal of Clinical ...
... an autosomal recessive disorder of unregulated and high insulin secretion. Mutations have also been associated with non-insulin ... diabetes mellitus type II, an autosomal dominant disease of defective insulin secretion. Alternative splicing of this gene has ... 1995). "Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion". Science. 268 (5209): ... 1998). "Decreased tolbutamide-stimulated insulin secretion in healthy subjects with sequence variants in the high-affinity ...
"Glucoregulatory mechanisms following hypophysectomy in diabetic dogs with residual insulin secretion". Diabetes. 32: 26-34. doi ... Implications for diabetes". Diabetes. 51 (Suppl 1): S271-S283. doi:10.2337/diabetes.51.2007.s271. Kaniuk NA, Kiraly M, Bates HE ... He was also the first to quantify the physiological secretion of insulin. Vranic was the first to establish the critical role ... Diabetes reflects insulin deficiency and glucagon abundance. Vranic discovered extrapancreatic glucagon in dogs, which changed ...
"Effect of the antipsychotic agent amisulpride on glucose lowering and insulin secretion". Diabetes, Obesity & Metabolism. 14 (4 ... diabetes, and risk of metabolic syndrome; this is most pronounced with olanzapine, while risperidone and quetiapine are also ...
... stimulates the secretion of insulin by the pancreas. It is not routinely used due to a higher incidence of adverse ... at a time when the primary medical treatment for diabetes was insulin injections. Eli Lilly had a lock on the market for ... Diabetes Prevention Program Research Group. "Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or ... It did this by changing the mindset about diabetes even more than insulin had. Treatment of this chronic disease was no longer ...
Postprandial hyperglycemia (PPHG) is primarily due to first phase insulin secretion. Alpha glucosidase inhibitors delay glucose ... Voglibose was first launched in 1994, under the trade name BASEN, to improve postprandial hyperglycemia in diabetes mellitus. ... is an alpha-glucosidase inhibitor used for lowering post-prandial blood glucose levels in people with diabetes mellitus. ...
"Glucagon-like peptide 1-potentiated insulin secretion and proliferation of pancreatic β-cells". J Diabetes. 6 (5): 394-402. doi ... Considered almost as important to the insulin secretion effects, GLP-1 has shown to inhibit glucagon secretion at glucose ... GLP-1 ensures the β cell insulin stores are replenished to prevent exhaustion during secretion by promoting insulin gene ... 2013). "Secretion of glucagon-like peptide-1 in patients with type 2 diabetes mellitus: systematic review and meta-analyses of ...
The secretion of insulin and the body's response to insulin decrease by 30%. Sleep deprivation also alters the productions of ... "Sleep Duration as a Risk Factor for the Development of Type 2 Diabetes or Impaired Glucose Tolerance: Analyses of the Quebec ... The secretion of insulin and the body's response to insulin decrease by 30%. Sleep deprivation also alters the productions of ... They needed more insulin to get rid of the same amount of glucose. If the body does not release more insulin to compensate, the ...
... has also been shown to regulate incretin and insulin hormone secretion. As a result, new drugs acting on the receptor ... Jones RM, Leonard JN, Buzard DJ, Lehmann J (Oct 2009). "GPR119 agonists for the treatment of type 2 diabetes". Expert Opinion ... "Endogenous and synthetic agonists of GPR119 differ in signalling pathways and their effects on insulin secretion in MIN6c4 ... Swaminath G (Dec 2008). "Fatty acid binding receptors and their physiological role in type 2 diabetes". Archiv der Pharmazie. ...
Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus". Lancet. 1 (7285): 785-9. doi:10.1016/ ... Fatty acids may act directly upon the pancreatic β-cell to regulate glucose-stimulated insulin secretion. This effect is ... It is theorized to play a role in explaining type 2 diabetes and insulin resistance. It was named for Philip Randle, who ... Grill V, Qvigstad E (2000). "Fatty acids and insulin secretion". British Journal of Nutrition. 83: S79-S84. doi:10.1017/ ...
2009). "Regulation of PKD by the MAPK p38delta in insulin secretion and glucose homeostasis". Cell. 136 (2): 235-48. doi: ... 2010). "Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction ... Assessment with ramipril and rosiglitazone Medication (DREAM) study". Diabetes Care. 33 (10): 2250-3. doi:10.2337/dc10-0452. ...
2009). "Genetic variability of procolipase associates with altered insulin secretion in non-diabetic Caucasians". Exp. Clin. ... Diabetes. 117 (2): 83-7. doi:10.1055/s-2008-1078733. PMID 18726866. Crandall WV, Lowe ME (2001). "Colipase residues Glu64 and ... of the pancreatic colipase gene and type 2 diabetes mellitus in two independent Caucasian study populations". Mol Nutr Food Res ...
Sulfonylurea drugs (SUs), widely used for the treatment of type 2 diabetes through stimulation of insulin secretion from ... "Role of Epac2A/Rap1 signaling in interplay between incretin and sulfonylurea in insulin secretion". Diabetes. 64 (4): 1262-72. ... Activation of cAMP signaling amplifies insulin secretion by Epac2-dependent as well as PKA-dependent pathways. Epac2-Rap1 ... Studies of Epac2 knockout mice indicate that Epac-mediated signaling is required for potentiation of insulin secretion by ...
The Hypophysis and Secretion of Insulin. Journal of Experimental Medicine, New York, 1942, 75: 547-566. Houssay, B. A.; Foglia ... Houssay demonstrated in the 1930s the diabetogenic effect anterior hypophysis extracts and the decrease in diabetes severity ... "The Hypophysis and Secretion of Insulin". The Journal of Experimental Medicine. 75 (5): 547-66. doi:10.1084/jem.75.5.547. PMC ... The Role of the Hypophysis in Carbohydrate Metabolism and in Diabetes. Nobel Prize lecture, 1947. ...
The hallmarks of Type II Diabetes (T2DM) pathogenesis are insulin resistance and impaired insulin secretion. In the earlier ... As a result, insulin secretion is ramped up, to try to compensate for this lack of response. For a while this may work, but ... Type II Diabetes is a progressive disease which eventually can lead to patients becoming dependent on exogenous insulin to ... Macdonald, I. A. (2016-11-01). "A review of recent evidence relating to sugars, insulin resistance and diabetes". European ...
December 2002). "Stimulus/secretion coupling factors in glucose-stimulated insulin secretion: insights gained from a ... Molecular and metabolic mechanisms of insulin resistance and β-cell failure in type 2 diabetes". Nature Reviews Molecular Cell ... This cycle is usually studied in relation to Glucose Stimulated Insulin Secretion ( or GSIS ) and there is thought to be a ... May 2008). "Chronic Suppression of Acetyl-CoA Carboxylase 1 in β-Cells Impairs Insulin Secretion via Inhibition of Glucose ...
Exubera (inhalable insulin) for diabetes, and insulin therapies. Flagyl (metronidazole) for bacterial and protozoal infections ... Genotropin (Growth hormone) for growth failure due to an inadequate secretion of endogenous growth hormone. Geodon (ziprasidone ...
These studies led to research on the effects in nondiabetic patients of an excessive secretion of insulin and his recognition ... Shortly after the discovery of insulin in 1922, Harris visited Canada to study diabetes cases with the scientists who ... 1934: Nomenclature of Disorders of Insulin Secretion, Annals of Internal Medicine 7(9): 1084-1100. 1936: The Diagnosis and ... Insulin and Diet In The Treatment of Diabetes, J. B. Lippincott & Co.. 1924: "Hyperinsulinism and Dysinsulinism", Journal of ...
"Sequence of human galanin and its inhibition of glucose-stimulated insulin secretion from RIN cells". Diabetes. 41 (1): 82-7. ... porcine and rat galanin inhibit glucose-induced insulin secretion in rats and dogs but have no effect on insulin secretion in ... doi:10.2337/diabetes.41.1.82. PMID 1370155. Gai WP, Geffen LB, Blessing WW (Aug 1990). "Galanin immunoreactive neurons in the ...
"Dietary and genetic control of glucose transporter-2 glycosylation promotes insulin secretion in suppressing diabetes". Cell. ... with type 2 diabetes and was responsible for a significant amount of insulin resistance present in obesity-associated diabetes ... Marth's laboratory has also taken a close look at the molecular and cellular bases of type 2 diabetes and the role that protein ... Ohtsubo, K.; Chen, M. Z.; Olefsky, J.M.; Marth, J.D. (2011). "Pathway to diabetes through attenuation of pancreatic beta cell ...
... only a minor defect in insulin secretion and others with slight insulin resistance and primarily a lack of insulin secretion.[ ... Type 2 diabetes is due to insufficient insulin production from beta cells in the setting of insulin resistance.[13] Insulin ... Type 2 diabetes. Other names. Diabetes mellitus type 2;. adult-onset diabetes;[1]. noninsulin-dependent diabetes mellitus ( ... "Monogenic Forms of Diabetes: Neonatal Diabetes Mellitus and Maturity-onset Diabetes of the Young". National Diabetes ...
Polyuria- Excessive secretion of urine.. Type I diabetes- Also called juvenile diabetes. Type I diabetes typically begins early ... Diabetes mellitus- Disease characterized by the inability of the body to produce or respond properly to insulin, required by ... Type II diabetes- Type II diabetes is the most common form of diabetes and usually appears in middle aged adults. It is often ... Insulin- A hormone secreted by the pancreas in response to high blood sugar levels that induces hypoglycemia. Insulin regulates ...
... in the β-cell is required for understanding the abnormalities of insulin secretion that occur in non-insulin-dependent diabetes ... Ion Channels and Insulin Secretion. Arun S Rajan, Lydia Aguilar-Bryan, Daniel A Nelson, Gordon C Yaney, Walter H Hsu, Diana L ... Ion Channels and Insulin Secretion. Arun S Rajan, Lydia Aguilar-Bryan, Daniel A Nelson, Gordon C Yaney, Walter H Hsu, Diana L ... We review the role of ion channels in regulating insulin secretion from pancreatic β-cells. By controlling ion permeability, ...
Intracellular Calcium Levels in Patients with Type 2 Diabetes, First-Degree Relatives of Patients with Type 2 Diabetes, and Age ... 2020 by the American Diabetes Association. Diabetes Print ISSN: 0012-1797, Online ISSN: 1939-327X. ... Your Name) has forwarded a page to you from Diabetes Message Body (Your Name) thought you would like to see this page from the ... Thank you for your interest in spreading the word about Diabetes.. NOTE: We only request your email address so that the person ...
2018 by the American Diabetes Association. Diabetes Print ISSN: 0012-1797, Online ISSN: 1939-327X. ... Your Name) has forwarded a page to you from Diabetes Message Body (Your Name) thought you would like to see this page from the ... Thank you for your interest in spreading the word about Diabetes.. NOTE: We only request your email address so that the person ... Diabetes Jun 2017, 66 (Supplement 1) A565-A584; DOI: 10.2337/db17-2153-2234 ...
A cellular protein from a family involved in several human diseases is crucial for the proper production and release of insulin ... Protein Critical For Insulin Secretion May Be Contributor To Diabetes. Published Wednesday 28 October 2009 Published Wed 28 Oct ... "Protein Critical For Insulin Secretion May Be Contributor To Diabetes." Medical News Today. MediLexicon, Intl., 28 Oct. 2009. ... "We know that Type 2 diabetes is a progressive illness where insulin secretion is high and then goes down over time, but why ...
In addition, glucose stimulates insulin secretion directly and potentiates... ... glucose serves to regulate basal insulin secretion by its participation with insulin in a feedback loop. ... In patients with long-standing insulin-dependent diabetes mellitus (IDDM), basal insulin secretion and insulin responses to all ... Pathophysiology of insulin secretion in noninsulin dependent diabetes mellitus, Diabetes Care 7: 491-502 (1984).PubMedCrossRef ...
... and find that a mislocalized calcium channel contributes to the failed insulin secretion associated with the disease. ... Mislocalized calcium channel causes insulin secretion defect in diabetes Press release. 2017-05-19 ... which causes secretion to fail. The findings offer a first glimpse at the intricate relationship between the insulin secretion ... In type-2 diabetes, the channel proteins that allow calcium the entry are instead located too far away from the insulin ...
... A research team at the University of California, Los ... Adult-onset diabetes is characterized by high blood glucose and the presence of insulin resistance. Between the years 1990 and ... blocking proper insulin secretion.. Taking the present study along with the known properties of toxic IAPP oligomers to induce ... Patients with type 2 diabetes have a decreasing number of beta cells, which are found in the pancreas and normally secrete ...
... and its been known for some time that this pulsatile insulin release is lost in people with type 2 diabetes. But no one knew ... They first put beta cells from mice in a high-glucose environment and found that they lost the pulsatile insulin secretion. ... In nondiabetics, insulin isnt secreted continuously but in pulses, ... postulate that its oscillating pulses of glucose that cause the oscillating pulses of insulin that are seen in healthy people ...
A plant-based diet improves the secretion of insulin and incretin hormones in those with type 2 diabetes, according to new ... A plant-based diet improves the secretion of insulin and incretin hormones in those with type 2 diabetes, according to new ... Plant-Based Meals Improve Insulin and Incretin Secretion in Those with Type 2 Diabetes ... postprandial secretion of insulin increased more after the plant-based meal than the meat-based meal. Secretion of incretin ...
Heterogeneous Contribution of Insulin Sensitivity and Secretion Defects to Gestational Diabetes Mellitus ... Heterogeneous Contribution of Insulin Sensitivity and Secretion Defects to Gestational Diabetes Mellitus ... Heterogeneous Contribution of Insulin Sensitivity and Secretion Defects to Gestational Diabetes Mellitus ... Heterogeneous Contribution of Insulin Sensitivity and Secretion Defects to Gestational Diabetes Mellitus ...
... in seven patients with gestational diabetes mellitus (GDM) and in eight age- and weight-matched nondiabetic pregnant women ... We have determined prehepatic insulin secretion rates (ISRs) ... Insulin secretion during and after pregnancy in patients with ... We have determined prehepatic insulin secretion rates (ISRs) in seven patients with gestational diabetes mellitus (GDM) and in ... Postpartum, insulin resistance and ISRs (and plasma insulin levels) improved in both groups, and ISRs (and plasma insulin ...
Diabetes Drug Reduces Insulin Secretion of β-Cells. Last Updated: May 11, 2009. ... The effect of pioglitazone on insulin secretion could be reversed by an AMPK inhibitor. The antidiabetic agents metformin and ... The antidiabetic drug pioglitazone may preserve pancreatic β-cell function by reducing insulin secretion at intermediate ... The researchers found that pioglitazone treatment led to a reduction in insulin secretion at intermediate glucose ...
... and find that a mislocalized calcium channel contributes to the failed insulin secretion associated with the disease. ... Mislocalized calcium channel causes insulin secretion defect in diabetes. May 19, 2017. Researchers from Uppsala University ... Related Diabetes Articles:. The role of vitamin A in diabetes. There has been no known link between diabetes and vitamin A -- ... Can continuous glucose monitoring improve diabetes control in patients with type 1 diabetes who inject insulin. Two studies in ...
Diabetes.co.uk © 2018 Diabetes Digital Media Ltd - the global diabetes community.. ... Insulin secretion In the December 2009 issue of the European Journal of Pharmacology, researchers reported that two different ... Diabetes Forum App Find support, ask questions and share your experiences with 281,823 members of the diabetes community. ... How does diabetes affect the body? Knowing how diabetes affects your body can help you look after your body ...
Beta cell dysfunction in maturity-onset diabetes: reversible loss of glucose-induced insulin secretion with retention of ...
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Exp Clin Endocrinol Diabetes. 1999;107(2):140-7. Research Support, Non-U.S. Govt ... lowest tertile for insulin sensitivity) was 40% in first degree relatives of patients with type 2 diabetes. Insulin secretion ... Exp Clin Endocrinol Diabetes. 1999;107(2):140-7.. Insulin action and secretion in healthy, glucose tolerant first degree ... Early phase relative insulin secretion (30 min) expressed as x-fold increase above basal was smaller in insulin resistant first ...
Many forms of diabetes mellitus display impaired glucose-induced insulin secretion. This has been shown to be the primary cause ... Insulin is stored in secretory granules in the beta-cell and is secreted by exocytosis. This process is precisely controlled to ... Beta-cell mitochondria in the regulation of insulin secretion: a new culprit in type II diabetes Diabetologia. 2000 Mar;43(3): ... Many forms of diabetes mellitus display impaired glucose-induced insulin secretion. This has been shown to be the primary cause ...
"We know that Type 2 diabetes is a progressive illness where insulin secretion is high and then goes down over time, but why ... as the disruption of insulin production and secretion resembles cellular effects seen in adult-onset diabetes. " ... "Its pro-insulin rather insulin, if anythings released at all." A mutation in the function of ClC-3 in humans could very well ... The study, "The Granular Chloride Channel ClC-3 Is Permissive for Insulin Secretion," was published in the journal Cell ...
Osmoregulation of thirst and vasopressin secretion in insulin-dependent diabetes mellitus C. J. Thompson C. J. Thompson ... Osmoregulation of thirst and vasopressin secretion in insulin-dependent diabetes mellitus. Clin Sci (Lond) 1 June 1988; 74 (6 ... As hyperglycaemia was not dipsogenic, however, the thirst of poorly controlled diabetes mellitus may be due to hypovolaemia ... 3. Drinking rapidly abolished thirst and vasopressin secretion before major changes in plasma osmolality occurred in both ...
"This is important as Type-2 diabetes is increasing to epidemic proportions worldwide. It is caused by defective insulin release ... In order to understand the disease its important to learn about the mechanism that control insulin secretion," says lead ... "However the mechanisms controlling insulin secretion have not been fully understood." The latest research in Professor ... can impair insulin secretion, as TCF7L2 redirects beta-catenin away from the cell surface and so would reduce the effect of ...
The journal welcomes submissions focusing on the epidemiology, etiology, pathogenesis, management, and prevention of diabetes, ... and clinical studies related to type 1 and type 2 diabetes. ... Journal of Diabetes Research is a peer-reviewed, Open Access ... Type 2 diabetes mellitus is a heterogeneous disease characterized by insulin resistance and defective insulin secretion [1]. ... ISI is greatly affected by the insulin secretion ability, and if the insulin secretion ability is decreased, ISI shows low ...
Treatment Differences Between Canagliflozin and Placebo in Insulin Secretion in Subjects With Type 2 Diabetes Mellitus (T2DM). ... Diabetes Mellitus. Diabetes Mellitus, Type 2. Insulin Resistance. Glucose Metabolism Disorders. Metabolic Diseases. Endocrine ... Diabetes Mellitus, Type 2. Metformin. Canagliflozin. INVOKANA®. Insulin sensitivity. DPP-4 inhibitor. dipeptidyl peptidase-4. ... Change from baseline in insulin secretion rate (ISR) during mixed-meal tolerance test (MMTT) [ Time Frame: Baseline, 25 weeks ] ...
Treatment Differences Between Canagliflozin and Placebo in Insulin Secretion in Subjects With Type 2 Diabetes Mellitus (T2DM). ...
  • Older Americans with diabetes born in the 1940s are living longer and with less disability performing day to day tasks than those born 10 years earlier, according to new research published in The Lancet Diabetes & Endocrinology journal. (brightsurf.com)
  • Elizabeth R. Seaquist , MD, Pennock Family Chair in Diabetes Research, Vice Chair for Clinical Affairs, and Director of the Division of Endocrinology and Diabetes at the University of Minnesota , presented information about the gender gaps that exist in the clinical sciences, with a focus on looking at advancement and rewards for women. (prnewswire.com)
  • The Omnipod closed-loop system is an 'untethered' patch pump with no tubing, which is very attractive to some patients," said chief investigator Bruce A. Buckingham, MD, professor of pediatrics, endocrinology and diabetes at Stanford University School of Medicine. (diabetes.org)
  • Professor in Diabetes & Endocrinology, Developmental Origins of Health and Disease Division, University of Southampton School of Medicine, Southampton, UK. (wiley.com)
  • Furthermore, we did not observe significant changes in insulin sensitivity in this cohort despite significant reductions in [subcutaneous adipose tissue] and liver fat content. (diabetes.co.uk)
  • Furthermore, the impact of the interaction between genetic variation in TCF7L2 and glycemia on changes in insulin secretion was tested in 315 individuals taking part in a lifestyle intervention study. (cdc.gov)
  • compared residual glucose-dependent insulin secretion and whole-genome RNA sequencing of islet tissue from donors with and without diabetes. (diabetesincontrol.com)
  • Glucose-stimulated insulin secretion from islet β cells is mediated by K ATP channels. (edu.au)
  • These findings support a mechanism by which the activation of resident islet macrophages and the intraislet release of IL-1 may mediate the initial dysfunction and destruction of β cells during the development of autoimmune diabetes. (jimmunol.org)
  • It has been suggested that resident islet macrophages may play a primary role in mediating the initial destruction of β cells during the development of autoimmune diabetes ( 1 ). (jimmunol.org)
  • 5 , 6 ) first showed that treatment of rat islets with IL-1 results in a potent inhibition of insulin secretion followed by islet destruction. (jimmunol.org)
  • Inhibitors of iNOS, N G -monomethyl- l -arginine (NMMA), aminoguanidine (AG), and nitro- l -arginine methylester prevent the inhibitory effects of IL-1 on insulin secretion and the destructive effects of IL-1 on islet viability ( 7 , 8 , 11 , 12 , 13 , 14 ). (jimmunol.org)
  • The β cell, selectively destroyed during the development of autoimmune diabetes, appears to be the sole islet cellular source of iNOS following treatment with IL-1. (jimmunol.org)
  • Moreover, high levels of glutamate, GABA, and glutamine and their respective vesicular and plasma membrane transporters have been shown in the islet cells and there is emerging support for these amino acids and their transporters playing important roles in the maturation and secretion of insulin and glucagon. (frontiersin.org)
  • However, neurons may also release insulin, and compelling evidence have been provided for a brain-centered glucoregulatory system that work in concert with the islet cells to regulate plasma levels of glucose ( 1 - 3 ). (frontiersin.org)
  • Islet adaptation to insufficient insulin involves compensatory changes in not only beta cells, but also in pancreatic alpha cells [ 2 ] [ 3 ]. (medsci.org)
  • Even transiently elevated glucose levels can cause volume and electrolyte abnormalities, delayed gastric emptying, impaired leukocyte function, osmotic diuresis and impaired insulin responses. (aafp.org)
  • The American Diabetes Association® (Association) will present the 2017 Outstanding Achievement in Clinical Diabetes Research Award to William V. Tamborlane, MD. This award recognizes exceptional contributions in patient-oriented or clinical outcomes research that have had a significant impact on diabetes prevention and treatment. (diabetes.org)
  • The American Diabetes Association's 77th Scientific Sessions, to be held June 9-13, 2017, at the San Diego Convention Center, is the world's largest scientific meeting focused on diabetes research, prevention and care. (diabetes.org)
  • This newly discovered signalling pathway may explain how one of the major diabetes susceptibility genes, called TCF7L2 , can impair insulin secretion, as TCF7L2 redirects beta-catenin away from the cell surface and so would reduce the effect of beta-catenin on insulin secretion. (healthcanal.com)
  • An animal study demonstrated that exposure to excess AGEs activates pathways of β -cell damage which, via mitochondrial superoxide generation, can impair insulin secretion [ 4 ]. (hindawi.com)
  • In order to understand the disease it's important to learn about the mechanism that control insulin secretion," says lead researcher Dr Emmanuelle Cognard, also from The University of Auckland. (healthcanal.com)
  • In addition to its classical role as a promoter of gluconeogenesis and glycogenolysis, glucagon, as well as GLP-1, are known to be stimulators of insulin release in beta cell lines and pancreatic islets [ 15 - 17 ]. (medsci.org)
  • Since many diabetic patients still exhibit poor glycemic control, other fail to respond to the treatment, and some develop serious complications, more effective treatments for diabetes than those mentioned above remain challenging for modern research. (eurekaselect.com)
  • 13 , 14 Furthermore, intensive diabetes team interventions during hospitalization have improved glycemic control and decreased the length of hospital stays. (aafp.org)
  • 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. (nature.com)
  • The granule membrane is recycled to the Golgi apparatus following release of insulin. (diapedia.org)
  • In the December 2009 issue of the European Journal of Pharmacology, researchers reported that two different ginger extracts, spissum and an oily extract, interact with serotonin receptors to reveres their effect on insulin secretion. (diabetes.co.uk)