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.Glucose Transporter Type 1: 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.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.Monosaccharide Transport Proteins: A large group of membrane transport proteins that shuttle MONOSACCHARIDES across CELL MEMBRANES.Glucose Transporter Type 3: A major glucose transporter found in NEURONS.Glucose Transporter Type 5: A hexose transporter that mediates FRUCTOSE transport in SKELETAL MUSCLE and ADIPOCYTES and is responsible for luminal uptake of dietary fructose in the SMALL INTESTINE.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.Vesicular Monoamine Transport Proteins: A family of vesicular amine transporter proteins that catalyze the transport and storage of CATECHOLAMINES and indolamines into SECRETORY VESICLES.Excitatory Amino Acid Transporter 3: A neuronal and epithelial type glutamate plasma membrane transporter protein.Tetrabenazine: A drug formerly used as an antipsychotic and treatment of various movement disorders. Tetrabenazine blocks neurotransmitter uptake into adrenergic storage vesicles and has been used as a high affinity label for the vesicle transport system.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).Glycine Plasma Membrane Transport Proteins: A family of sodium chloride-dependent neurotransmitter symporters that transport the amino acid GLYCINE. They differ from GLYCINE RECEPTORS, which signal cellular responses to GLYCINE. They are located primarily on the PLASMA MEMBRANE of NEURONS; GLIAL CELLS; EPITHELIAL CELLS; and RED BLOOD CELLS where they remove inhibitory neurotransmitter glycine from the EXTRACELLULAR SPACE.Glutamate Plasma Membrane Transport Proteins: A family of plasma membrane neurotransmitter transporter proteins that couple the uptake of GLUTAMATE with the import of SODIUM ions and PROTONS and the export of POTASSIUM ions. In the CENTRAL NERVOUS SYSTEM they regulate neurotransmission through synaptic reuptake of the excitatory neurotransmitter glutamate. Outside the central nervous system they function as signal mediators and regulators of glutamate metabolism.Glucose Transport Proteins, Facilitative: A family of monosaccharide transport proteins characterized by 12 membrane spanning helices. They facilitate passive diffusion of GLUCOSE across the CELL MEMBRANE.Sarcosine: An amino acid intermediate in the metabolism of choline.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.Amino Acid Transport System X-AG: A family of POTASSIUM and SODIUM-dependent acidic amino acid transporters that demonstrate a high affinity for GLUTAMIC ACID and ASPARTIC ACID. Several variants of this system are found in neuronal tissue.Vesicular Biogenic Amine Transport Proteins: Integral membrane proteins of the LIPID BILAYER of SECRETORY VESICLES that catalyze transport and storage of biogenic amine NEUROTRANSMITTERS such as ACETYLCHOLINE; SEROTONIN; MELATONIN; HISTAMINE; and CATECHOLAMINES. The transporters exchange vesicular protons for cytoplasmic neurotransmitters.Deoxyglucose: 2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity.Cytochalasin B: A cytotoxic member of the CYTOCHALASINS.Blood Glucose: Glucose in blood.3-O-Methylglucose: 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)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.MethylglucosidesSodium-Glucose Transporter 1: The founding member of the sodium glucose transport proteins. It is predominately expressed in the INTESTINAL MUCOSA of the SMALL INTESTINE.Muscle Proteins: The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.Membrane Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.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).Isoflurane: A stable, non-explosive inhalation anesthetic, relatively free from significant side effects.Organic Anion Transporters: Proteins involved in the transport of organic anions. They play an important role in the elimination of a variety of endogenous substances, xenobiotics and their metabolites from the body.PhlorhizinPositron-Emission Tomography: An imaging technique using compounds labelled with short-lived positron-emitting radionuclides (such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18) to measure cell metabolism. It has been useful in study of soft tissues such as CANCER; CARDIOVASCULAR SYSTEM; and brain. SINGLE-PHOTON EMISSION-COMPUTED TOMOGRAPHY is closely related to positron emission tomography, but uses isotopes with longer half-lives and resolution is lower.PhloretinCell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.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.Sodium-Glucose Transport Proteins: Monosaccharide transport proteins that function as active symporters. They utilize SODIUM or HYDROGEN IONS to transport GLUCOSE across CELL MEMBRANES.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.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.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.Kinetics: The rate dynamics in chemical or physical systems.Molecular 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.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.Monocarboxylic Acid Transporters: A family of proteins involved in the transport of monocarboxylic acids such as LACTIC ACID and PYRUVIC ACID across cellular membranes.Symporters: Membrane transporters that co-transport two or more dissimilar molecules in the same direction across a membrane. Usually the transport of one ion or molecule is against its electrochemical gradient and is "powered" by the movement of another ion or molecule with its electrochemical gradient.PropylaminesHexokinase: An enzyme that catalyzes the conversion of ATP and a D-hexose to ADP and a D-hexose 6-phosphate. D-Glucose, D-mannose, D-fructose, sorbitol, and D-glucosamine can act as acceptors; ITP and dATP can act as donors. The liver isoenzyme has sometimes been called glucokinase. (From Enzyme Nomenclature, 1992) EC Oxidase: An enzyme of the oxidoreductase class that catalyzes the conversion of beta-D-glucose and oxygen to D-glucono-1,5-lactone and peroxide. It is a flavoprotein, highly specific for beta-D-glucose. The enzyme is produced by Penicillium notatum and other fungi and has antibacterial activity in the presence of glucose and oxygen. It is used to estimate glucose concentration in blood or urine samples through the formation of colored dyes by the hydrogen peroxide produced in the reaction. (From Enzyme Nomenclature, 1992) EC 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.GlycogenAffinity Labels: Analogs of those substrates or compounds which bind naturally at the active sites of proteins, enzymes, antibodies, steroids, or physiological receptors. These analogs form a stable covalent bond at the binding site, thereby acting as inhibitors of the proteins or steroids.Serotonin Plasma Membrane Transport Proteins: Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of serotonergic neurons. They are different than SEROTONIN RECEPTORS, which signal cellular responses to SEROTONIN. They remove SEROTONIN from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS. Regulates signal amplitude and duration at serotonergic synapses and is the site of action of the SEROTONIN UPTAKE INHIBITORS.Biological Transport, Active: The movement of materials across cell membranes and epithelial layers against an electrochemical gradient, requiring the expenditure of metabolic energy.Dopamine Plasma Membrane Transport Proteins: Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of dopaminergic neurons. They remove DOPAMINE from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS and are the target of DOPAMINE UPTAKE INHIBITORS.Glycolysis: 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.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.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.Excitatory Amino Acid Transporter 2: A glutamate plasma membrane transporter protein found in ASTROCYTES and in the LIVER.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.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.Azides: Organic or inorganic compounds that contain the -N3 group.3T3-L1 Cells: 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.Cystinyl Aminopeptidase: A zinc-containing sialoglycoprotein that is used to study aminopeptidase activity in the pathogenesis of hypertension. EC Agents: Substances which lower blood glucose levels.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.Glycosides: Any compound that contains a constituent sugar, in which the hydroxyl group attached to the first carbon is substituted by an alcoholic, phenolic, or other group. They are named specifically for the sugar contained, such as glucoside (glucose), pentoside (pentose), fructoside (fructose), etc. Upon hydrolysis, a sugar and nonsugar component (aglycone) are formed. (From Dorland, 28th ed; From Miall's Dictionary of Chemistry, 5th ed)3T3 Cells: 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.Amino Acid Transport Systems: Cellular proteins and protein complexes that transport amino acids across biological membranes.Disaccharides: Oligosaccharides containing two monosaccharide units linked by a glycosidic bond.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Organic Cation Transporter 1: An organic cation transporter found in kidney. It is localized to the basal lateral membrane and is likely to be involved in the renal secretion of organic cations.Fructose: 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.Dehydroascorbic Acid: The reversibly oxidized form of ascorbic acid. It is the lactone of 2,3-DIKETOGULONIC ACID and has antiscorbutic activity in man on oral ingestion.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.Excitatory Amino Acid Transporter 1: A glial type glutamate plasma membrane transporter protein found predominately in ASTROCYTES. It is also expressed in HEART and SKELETAL MUSCLE and in the PLACENTA.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Nerve Tissue ProteinsLeishmania enriettii: A parasitic hemoflagellate of the subgenus Leishmania leishmania that has been found as a natural infection of the Brazilian guinea pig. Its host-tissue relationship is, in general, comparable to that of L. braziliensis.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 Mellitus, Experimental: Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Norepinephrine Plasma Membrane Transport Proteins: Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of noradrenergic neurons. They remove NOREPINEPHRINE from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS. It regulates signal amplitude and duration at noradrenergic synapses and is the target of ADRENERGIC UPTAKE INHIBITORS.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.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.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.Organic Anion Transporters, Sodium-Independent: A subclass of ORGANIC ANION TRANSPORTERS that do not rely directly or indirectly upon sodium ion gradients for the transport of organic ions.Cation Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of positively charged molecules (cations) across a biological membrane.Microsomes: Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)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.Organic Cation Transport Proteins: A family of proteins involved in the transport of organic cations. They play an important role in the elimination of a variety of endogenous substances, xenobiotics, and their metabolites from the body.Muscles: Contractile tissue that produces movement in animals.4-Chloromercuribenzenesulfonate: A cytotoxic sulfhydryl reagent that inhibits several subcellular metabolic systems and is used as a tool in cellular physiology.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.Nucleoside Transport Proteins: Proteins involved in the transport of NUCLEOSIDES across cellular membranes.Fasting: Abstaining from all food.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Xenopus laevis: The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.GABA Plasma Membrane Transport Proteins: A family of plasma membrane neurotransmitter transporter proteins that regulates extracellular levels of the inhibitory neurotransmitter GAMMA-AMINOBUTYRIC ACID. They differ from GABA RECEPTORS, which signal cellular responses to GAMMA-AMINOBUTYRIC ACID. They control GABA reuptake into PRESYNAPTIC TERMINALS in the CENTRAL NERVOUS SYSTEM through high-affinity sodium-dependent transport.Sodium-Glucose Transporter 2: A sodium-glucose transporter that is expressed in the luminal membrane of the PROXIMAL KIDNEY TUBULES.Glucose 1-Dehydrogenase: A glucose dehydrogenase that catalyzes the oxidation of beta-D-glucose to form D-glucono-1,5-lactone, using NAD as well as NADP as a coenzyme.Lactic Acid: A normal intermediate in the fermentation (oxidation, metabolism) of sugar. The concentrated form is used internally to prevent gastrointestinal fermentation. (From Stedman, 26th ed)Amino Acid Transport Systems, Neutral: Amino acid transporter systems capable of transporting neutral amino acids (AMINO ACIDS, NEUTRAL).Sodium-Coupled Vitamin C Transporters: Membrane transport proteins that actively co-transport ASCORBIC ACID and sodium ions across the CELL MEMBRANE. Dietary absorption of VITAMIN C is highly dependent upon this class of transporters and a subset of SODIUM GLUCOSE TRANSPORTERS which transport the oxidized form of vitamin C, DEHYDROASCORBIC ACID.Organic Anion Transporters, Sodium-Dependent: A subclass of ORGANIC ANION TRANSPORTERS whose transport of organic anions is driven either directly or indirectly by a gradient of sodium ions.Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable.Glucose-6-Phosphate: An ester of glucose with phosphoric acid, made in the course of glucose metabolism by mammalian and other cells. It is a normal constituent of resting muscle and probably is in constant equilibrium with fructose-6-phosphate. (Stedman, 26th ed)Oocytes: Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).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)Time Factors: Elements of limited time intervals, contributing to particular results or situations.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.Blotting, Northern: Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.Subcellular Fractions: Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)

Beta-cell gene expression and functional characterisation of the human insulinoma cell line CM. (1/340)

Animal insulinoma cell lines are widely used to study physiological and pathophysiological mechanisms involved in glucose metabolism and to establish in vitro models for studies on beta-cells. In contrast, human insulinoma cell lines are rarely used because of difficulties in obtaining and culturing them for long periods. The aim of our study was to investigate, under different experimental conditions, the capacity of the human insulinoma cell line CM to retain beta-cell function, particularly the expression of constitutive beta-cell genes (insulin, the glucose transporters GLUT1 and GLUT2, glucokinase), intracellular and secreted insulin, beta-cell granules, and cAMP content. Results showed that CM cells from an early-passage express specific beta-cell genes in response to glucose stimulation, in particular the insulin and GLUT genes. Such capacity is lost at later passages when cells are cultured at standard glucose concentrations. However, if cultured at lower glucose concentration (0.8 mM) for a longer time, CM cells re-acquire the capacity to respond to glucose stimulation, as shown by the increased expression of beta-cell genes (insulin, GLUT2, glucokinase). Nonetheless, insulin secretion could not be restored under such experimental conditions despite the presence of intracellular insulin, although cAMP response to a potent activator of adenylate cyclase, forskolin, was present indicating a viable system. In conclusion, these data show that the human insulinoma cell line CM, at both early-passage and late-passage, posseses a functional glucose-signalling pathway and insulin mRNA expression similar to normal beta-cells, representing, therefore, a good model for studies concerning the signalling and expression of beta-cells. Furthermore, we have previously shown that it is also a good model for immunological studies. In this respect it is important to note that the CM cell line is one of the very few existing human beta-cell lines in long-term culture.  (+info)

Sucrase-isomaltase and hexose transporter gene expressions are coordinately enhanced by dietary fructose in rat jejunum. (2/340)

We previously demonstrated that the levels of mRNAs of both sucrase-isomaltase (SI) and sodium/D-glucose transporter (SGLT1) are modulated by dietary sucrose in the rat jejunum. In the present study, we investigated whether the transcription of the gene coding SI is regulated by certain types of monosaccharides. Force-feeding a fructose and sucrose diet, (40% energy as fructose or sucrose) gave rise to parallel increases in the transcripts of SI and intestinal hexose transporters (SGLT1, GLUT5, and GLUT2) within 12 h. Force-feeding a glycerol-containing diet also caused an enhancement of SI, SGLT1, and GLUT2 mRNA levels. However, feeding the diet containing glucose or alpha-methylglucoside generally did not increase the transcript levels of SI or the intestinal hexose transporters. Nuclear run-on assays revealed that fructose as well as sucrose increased the transcription of both SI and GLUT5 genes and that the transcription rates of these genes were unaffected by glucose. These results suggest that fructose (or a metabolite) is capable of increasing the mRNA levels of SI and hexose transporters in the small intestine and that transcriptional regulation might play a pivotal role in the carbohydrate-induced coordinate enhancement of SI and fructose transporter gene expression  (+info)

Neonatal diabetes mellitus with hypergalactosemia. (3/340)

We report the case of a male, small-for-gestational-age newborn who presented with failure to thrive, severe fluctuation of blood glucose concentrations, and increased serum concentrations of galactose. The infant responded well to a lactose-free diet supplemented with fructose, inulin and corn starch. The metabolic disorder disappeared within 6 months. The transient course, and results of a molecular analysis of the glucose transporter 2 (Glut2) gene seem to rule out Fanconi-Bickel syndrome.  (+info)

Comparative aspects of the function and mechanism of SUR1 and MDR1 proteins. (4/340)

ATP-binding cassette (ABC) superfamily proteins have divergent functions and can be classified as transporters, channels, and receptors, although their predicted secondary structures are very much alike. Prominent members include the sulfonylurea receptor (SUR1) and the multidrug transporter (MDR1). SUR1 is a subunit of the pancreatic beta-cell K(ATP) channel and plays a key role in the regulation of glucose-induced insulin secretion. SUR1 binds ATP at NBF1, and ADP at NBF2 and the two NBFs work cooperatively. The pore-forming subunit of the pancreatic beta-cell K(ATP) channel, Kir6.2, is a member of the inwardly rectifying K(+) channel family, and also binds ATP. In this article, we present a model in which the activity of the K(ATP) channel is determined by the balance of the action of ADP, which activates the channel through SUR1, and the action of ATP, which stabilizes the long closed state by binding to Kir6.2. The concentration of ATP could also affect the channel activity through binding to NBF1 of SUR1. MDR1, on the other hand, is an ATP-dependent efflux pump which extrudes cytotoxic drugs from cells before they can reach their intracellular targets, and in this way confers multidrug resistance to cancer cells. Both NBFs of MDR1 can hydrolyze nucleotides, and their ATPase activity is necessary for drug transport. The interaction of SUR1 with nucleotides is quite different from that of MDR1. Variations in the interactions with nucleotides of ABC proteins may account for the differences in their functions.  (+info)

Maternal hypothyroxinemia influences glucose transporter expression in fetal brain and placenta. (5/340)

The influence of maternal hypothyroxinemia on the expression of the glucose transporters, GLUT1 and GLUT3, in rat fetal brain and placenta was investigated. Fetal growth was retarded in hypothyroxinemic pregnancies, but only before the onset of fetal thyroid hormone synthesis. Placental weights were normal, but placental total protein concentration was reduced at 19 days gestation (dg). Immunoblotting revealed a decreased abundance of GLUT1 in placental microsomes at 16 dg, whereas GLUT3 was increased. Fetal serum glucose levels were reduced at 16 dg. In fetal brain, the concentration of microsomal protein was deficient at 16 dg and the abundance of parenchymal forms of GLUT1 was further depressed, whereas GLUT3 was unaffected. Northern hybridization analysis demonstrated normal GLUT1 mRNA levels in placenta and fetal brain. In conclusion, maternal hypothyroxinemia results in fetal growth retardation and impaired brain development before the onset of fetal thyroid function. Glucose uptake in fetal brain parenchyma may be compromised directly, due to deficient GLUT1 expression in this tissue, and indirectly, as a result of reduced placental GLUT1 expression. Though corrected by the onset of fetal thyroid hormone synthesis, these deficits are present during the critical period of neuroblast proliferation and may contribute to long term changes in brain development and function seen in this model and in the progeny of hypothyroxinemic women.  (+info)

A dietary intervention (high carbohydrate) during the neonatal period causes islet dysfunction in rats. (6/340)

Artificial rearing of 4-day-old rat pups on a high-carbohydrate (HC) milk formula results in the immediate onset of hyperinsulinemia. To evaluate these early changes, studies on pancreatic function were carried out on 12-day-old HC rats and compared with age-matched mother-fed (MF) pups. The plasma insulin and glucagon contents were increased sixfold and twofold, respectively, in HC rats compared with MF rats. There was a distinct leftward shift in the glucose-stimulated insulin secretory pattern for HC islets. HC islets secreted insulin in the absence of any added glucose and in the presence of Ca(2+) channel inhibitors. The activities of glucokinase, hexokinase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate dehydrogenase complex were significantly increased in HC islets compared with MF islets. The protein contents of GLUT-2 and hexokinase were significantly increased in HC islets. These findings indicate that a nutritional intervention in the form of a HC formula only during the suckling period has a profound influence on pancreatic function, causing the onset of hyperinsulinemia.  (+info)

Insulin resistance and glucose transporter expression during the euglycemic hyperinsulinemic clamp in the lamb. (7/340)

Three- to six-day-old lambs infused with 100 mU x kg(-1) x min(-1) insulin required greater amounts of glucose to maintain euglycemia during a euglycemic hyperinsulinemic clamp compared with 31- to 35-day-old insulin-infused lambs (15.87 +/- 3.47 vs. 4.30 +/- 1.11 mg x kg(-1) x min(-1), P < 0.05, respectively). Endogenous glucose production persisted in both groups; however, the percent decrease compared with age-matched lambs receiving no insulin was greater in the younger group compared with the older group (53%, P < 0.001, vs. 34%, P < 0.01). The younger animals showed greater glucose utilization compared with the older animals (215 vs. 96%, respectively, P < 0.01). No effect of insulin was noted on GLUT-4 protein expression in either group. GLUT-2 expression was increased in older vs. younger lambs. Older insulin-infused lambs showed lower GLUT-2 expression than older 0 insulin-infused lambs [0.94 +/- 0.07 vs. 1.64 +/- 0.10 (OD) units, P < 0.005]. Increased sensitivity to insulin in the younger animals was not related to acute changes in GLUT-4 expression. Increased GLUT-2 expression with age, as well as decreased expression with hyperinsulinemia, is consistent with the development of an insulin-resistant state in the adult.  (+info)

The large intracytoplasmic loop of the glucose transporter GLUT2 is involved in glucose signaling in hepatic cells. (8/340)

The hypothesis that the glucose transporter GLUT2 can function as a protein mediating transcriptional glucose signaling was addressed. To divert the putative interacting proteins from a glucose signaling pathway, two intracytoplasmic domains of GLUT2, the C terminus and the large loop located between transmembrane domains 6 and 7, were transfected into mhAT3F hepatoma cells. Glucose-induced accumulation of two hepatic gene mRNAs (GLUT2 and L-pyruvate kinase) was specifically inhibited in cells transfected with the GLUT2 loop and not with the GLUT2 C terminus. The dual effects of glucose were dissociated in cells expressing the GLUT2 loop; in fact a normal glucose metabolism into glycogen occurred concomitantly with the inhibition of the glucose-induced transcription. This inhibition by the GLUT2 loop could be due to competitive binding of a protein that normally interacts with endogenous GLUT2. In addition, the GLUT2 loop, tagged with green fluorescent protein (GFP), was located within the nucleus, whereas the GFP and GFP-GLUT2 C-terminal proteins remained in the cytoplasm. In living cells, a fraction (50%) of the expressed GFP-GLUT2 loop translocated rapidly from the cytoplasm to the nucleus in response to high glucose concentration and conversely in the absence of glucose. We conclude that, via protein interactions with its large loop, GLUT2 may transduce a glucose signal from the plasma membrane to the nucleus.  (+info)

  • The major route for the transport of dietary glucose from intestinal lumen into enterocytes is the Na + /glucose cotransporter (SGLT1), although glucose transporter type 2 (GLUT2) may also play a role. (
  • A growing line of evidence suggests that cytosolic calcium ([Ca 2+ ] cyt ) can regulate the absorption of glucose by adjusting GLUT2 and SGLT1. (
  • This heterogeneity in glucose metabolism cannot be attributed to differences in GLUT2 mRNA levels or in glucose transport. (
  • For example, the polyphenol phloretin inhibits a protein called glucose transporter 2 (GLUT2) plays a role in advanced-stage cell growth in certain types of cancer . (
  • The sugar transporter GLUT2, present in several tissues of the gut-brain axis, has been reported to be involved in the control of food intake. (
  • GLUT2 is a sugar transporter sustaining energy production in the cell, but it can also function as a receptor for extracellular glucose. (
  • However, the contribution of the receptor function over the transporter function of GLUT2 in the control of food intake remains to be determined. (
  • Thus, we generated transgenic mice that express a GLUT2-loop domain, blocking the detection of glucose but leaving GLUT2-dependent glucose transport unaffected. (
  • Inhibiting GLUT2-mediated glucose detection augmented daily food intake by a mechanism that increased the meal size but not the number of meals. (
  • Our data provide evidence that glucose detection by GLUT2 contributes to the control of food intake by the hypothalamus. (
  • The sugar transporter receptor, i.e., "transceptor" GLUT2, may constitute a drug target to treat eating disorders and associated metabolic diseases, particularly by modulating its receptor function without affecting vital sugar provision by its transporter function. (
  • By contrast, GLUT2, a high-capacity, high- K m transporter isoform ( 6 ), when associated with an efficient glucokinase, sustains fluxes of higher glucose concentrations. (
  • GLUT2 is present in brain areas involved in the control of food intake, whereas the exact nature of GLUT2-expressing cells remains unclear since GLUT2 has been identified in neurons, astrocytes, and tanycytes ( 1 , 2 , 17 , 28 , 36 ). (
  • Nevertheless, it is not known whether GLUT2 is present in the glucose-sensitive neurons expressing orexigenic or anorexigenic peptides ( 26 ). (
  • Pdx1 has also been proposed to be a master regulator of β cell activity, in part based on the severe diabetic phenotype observed upon deletion of this factor from β cells in animals, a phenotype at least caused by reduced insulin and glucose transporter type 2 (GLUT2) expression ( 4 ). (
  • The present study compares glucose metabolism in two beta-cell subpopulations that have been separated on the basis of the presence (high responsive) or absence (low responsive) of a metabolic redox shift at 7.5 mM glucose. (
  • Early adaptive changes in hypertrophy include increased ventricular mass-to-cavity volume ratio (M/V ratio) and increased dependence on glucose for energy metabolism. (
  • In light of the potential role of glucose metabolism in maintaining contractile function during the progression of pressure-overload hypertrophy, we hypothesized that impaired glucose transport occurs early in the progression to ventricular dilatation. (
  • A glucose-signaling pathway is indeed triggered, independently of glucose metabolism, through its large cytoplasmic loop domain. (
  • Dr. Shulman's research is focused on understanding the regulation of glucose and fat metabolism in humans and its dysregulation in patients with T2DM. (
  • To this end, his group has developed several magnetic resonance spectroscopy (MRS) methods to examine intracellular glucose and fat metabolism non-invasively in humans. (
  • Hyper- and hypothyroidism have been associated with insulin resistance which has been reported to be the major cause of impaired glucose metabolism in T2DM. (
  • The phase 2 trial involved patients with glucose transporter type 1 deficiency syndrome (G1DS), a genetic defect in glucose metabolism which is linked to epileptic seizures and movement impairment. (
  • Metabolism is usually divided into two categories: catabolism, the breaking down of organic matter for example, the breaking down of glucose to pyruvate, by cellular respiration, and anabolism, the building up of components of cells such as proteins and nucleic acids. (
  • Amino acids also contribute to cellular energy metabolism by providing a carbon source for entry into the citric acid cycle (tricarboxylic acid cycle), especially when a primary source of energy, such as glucose, is scarce, or when cells undergo metabolic stress. (
  • When administered to type 2 diabetic subjects, these peptides exert multiple antidiabetogenic effects: they stimulate insulin secretion, they lower fasting concentrations of blood glucose, and they attenuate the elevation of blood glucose concentration that is typically observed following ingestion of a meal. (
  • Identification of Epac as an intermediary linking the GLP-1-R to the stimulation of insulin secretion has led to an appreciation that the blood glucose-lowering effect of GLP-1 might be reproduced using pharmacological agents that activate cAMPGEFs in a direct and selective manner. (
  • Protein expression levels of these transporters were confirmed by immunohistochemistry and Western blotting. (
  • We conclude that regulation by TCDD of glucose transport activity in mice is an aryl, hydrocarbon receptor-dependent process and that the adipose-type GLUT4 appears to be regulated at the mRNA level, whereas the brain-type GLUT1 is affected mainly at the protein level. (
  • Shelterin complex components are made up of six component proteins - telomere repeat-binding factor 1 (TRF1), TRF2, repressor/activator protein 1 (RAP1), TRF1-interacting nuclear protein 2 (TIN2), TIN2-interacting protein 1 (TPP1) and protection of telomeres 1 (POT1) - which are essential for telomere protection and for regulating telomere elongation. (
  • Glucose transporter protein expression was the same in all groups. (
  • A glucose sensitive regulator of insulin transcription includes a glucose response element (GIRE) of a liver-pyruvate (L-PK) gent promoter, and an insulin-sensitive element of an insulin-like growth factor binding protein-1 (IGFBP-1) basal promoter. (
  • said glucose response element is inserted upstream of said insulin-sensitive element in an insulin-like growth factor binding protein-1 (IGFBP-1) basal promoter. (
  • The protein encoded by this gene is a transcriptional activator of several genes, including insulin, somatostatin, glucokinase, islet amyloid polypeptide, and glucose transporter type 2. (
  • The encoded nuclear protein is involved in the early development of the pancreas and plays a major role in glucose-dependent regulation of insulin gene expression. (
  • Solute carrier family 2, facilitated glucose transporter member 10 is a protein that in humans is encoded by the SLC2A10 gene. (
  • Translocator protein (TSPO), formerly known as peripheral-type benzodiazepine receptor (PBR), has been described in several tissues and characterized as one of the main elements of steroidogenesis. (
  • These pathways include protein kinase A (PKA), Ca 2+ /calmodulin-regulated protein kinase (CaMK), mitogen-activated protein kinases (MAPK, ERK1/2), phosphatidylinositol 3-kinase (PI-3K), protein kinase B (PKB, Akt ), and atypical protein kinase C-ζ (PKC-ζ). (
  • Cohort 1 had 823 patients with hypertension participating in a 12-week randomized ambulatory BP monitoring trial with mean (SD) age 60.2 (9.0) yrs, HbA1c 7.9 (0.7)%, office systolic BP (SBP) 142 (12) mmHg and BMI 32.6 (5.1) kg/m 2 . (
  • Cohort 2 pooled 2476 patients from four 24-week phase III randomized trials with age 55.6 (10.2) yrs, HbA1c 8.0 (0.9)%, office SBP 129 (15) mmHg and BMI 28.7 (5.5) m/kg 2 . (
  • Previous studies have demonstrated that every 1% decrease in hemoglobin A1C (HbA1C) is associated with a 35% reduction in the risk of microvascular complications (2). (
  • A healthy lifestyle such as diet, exercise and weight control can provide the foundation for managing of T 2 DM, however anti-diabetic agents are required to regulate blood glucose levels in the serious conditions. (
  • These antioxidants have been proposed as potential anti-diabetic drugs by acting as biological targets involved in T 2 DM development. (
  • Moreover, we highlighted the anti-diabetic effects of the flavonoids in the management of T 2 DM, through modulating glucose transporters, with particular emphasis on the investigations and recent findings. (
  • The aim of the present study was to examine the effects of pyrrolidine dithiocarbamate (PDTC) on hepatic glycogen synthesis and FoxO1 transcriptional activity in type 2 diabetic rats and the mechanism underlying these effects. (
  • Magnesium upregulates insulin receptor and glucose transporter-4 in streptozotocin-nicotinamide-induced type-2 diabetic rats. (
  • Molecular Interaction of Anti-Diabetic Drugs With Acetylcholinesterase (show AChE ELISA Kits ) and Sodium Glucose Co-Transporter 2. (
  • The current literature on cardiovascular event rates in type 2 diabetic patients is summarized as follows. (
  • The macrovascular event rate in type 2 diabetic patients was found to be on par with being a cardiovascular disease risk equivalent (~20% at 10 years). (
  • ABCG8 polymorphisms and renal disease in type 2 diabetic patients. (
  • T 2 DM affects several major organs, including heart, blood vessels, nerves, eyes and kidneys leading to disabling or even life-threatening complications such as cardiac dysfunction, atherosclerosis, and nephropathy [ 7 ]. (
  • In severely hyperglycemic patients, the kidneys play a protective role by excreting the excess filtered glucose load. (
  • It lowers blood sugar by increasing glucose the kidneys excrete. (
  • The antidiabetic potential of flavonoids are mainly through their modulatory effects on glucose transporter by enhancing GLUT-2 expression in pancreatic β cells and increasing expression and promoting translocation of GLUT-4 via PI3K/AKT, CAP/Cb1/TC10 and AMPK pathways. (
  • Immunoblotting for the adipose-type (type 4) glucose transporter (GLUT) showed a 40% decrease in the membrane fraction of adipose tissue from C57BL/6 mice treated with 116 micrograms/kg TCDD for 40 hr. (
  • This means that the specific radioactive imaging probe for SGLTs, α-methyl-4-deoxy-4-[ 18 F]fluoro- d -glucopyranoside, may be used along with positron-emission tomography to diagnose and stage pancreatic and prostate cancers, tumors in which the GLUT probe 2-[ 18 F]fluoro-2-deoxy- d -glucose has questionable utility. (
  • Phosphorylated by the SAPK2 pathway at high intracellular glucose concentration. (
  • Poor blood glucose control and its associated risk factors resulting in disabling complications will have a catastrophic impact on patients with T2DM, their families, society, the healthcare system and the economy. (
  • Despite the wide range of antihyperglycemic drugs available, current therapeutic strategies fall short of optimal glycemic control, especially in patients with long-standing T2DM with complications and/or multiple cardiovascular disease risk factors ( 2 , 3 ). (
  • The most probable mechanism leading to T2DM in thyroid dysfunction could be attributed to perturbed genetic expression of a constellation of genes along with physiological aberrations leading to impaired glucose utilization and disposal in muscles, overproduction of hepatic glucose output, and enhanced absorption of splanchnic glucose. (
  • T2DM is a progressive disease which can lead to numerous macrovascular complications such as myocardial infarction, amputation, stroke, as well as microvascular complications such as nephropathy, retinopathy, and neuropathy (2). (
  • Therefore, it is crucial that glucose levels in patients diagnosed with T2DM are adequately controlled. (
  • Both insulin resistance and deficiency leads to hyperglycemia due to altered glucose transport into the cells. (
  • In adipose tissue a slight recovery was observed by 30 days, but in the brains of treated animals glucose transport was significantly decreased even at the latest time. (
  • Simultaneously, qRT-PCR results revealed that 2.0 mol/L API-2 treatment significantly downregulated the mRNA pattern of MuERV-L and eIF-1A, two marker genes of ZGA, suggesting a defect in ZGA compared with that of control group. (
  • May also participate with the Na(+)/glucose cotransporter in the transcellular transport of glucose in the small intestine and kidney. (
  • The MFS signature sequence, which occurs in the hydrophilic loop that separates TM2 and TM3, is the most highly conserved sequence in this transporter superfamily. (
  • Flavonoids have antioxidative properties which protect the body against the deleterious effects of hyperglycemia in T 2 DM, through acting on the biological targets such as α-glucosidase, glucose co-transporter or aldose reductase. (
  • Inhibition of phosphorylated Ser473-Akt from translocating into the nucleus contributes to 2-cell arrest and defective zygotic genome activation in mouse preimplantation embryogenesis. (