Biomaterial Database

Sulfonylurea receptor type 1 knock-out mice have intact feeding-stimulated insulin secretion despite marked impairment in their response to glucose. 2002

Chiyo Shiota, and Olof Larsson, and Kathy D Shelton, and Masakazu Shiota, and Alexander M Efanov, and Marianne Hoy, and Jill Lindner, and Suwattanee Kooptiwut, and Lisa Juntti-Berggren, and Jesper Gromada, and Per-Olof Berggren, and Mark A Magnuson

Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.

The ATP-sensitive potassium channel is a key molecular complex for glucose-stimulated insulin secretion in pancreatic beta cells. In humans, mutations in either of the two subunits for this channel, the sulfonylurea type 1 receptor (Sur1) or Kir6.2, cause persistent hyperinsulinemic hypoglycemia of infancy. We have generated and characterized Sur1 null mice. Interestingly, these animals remain euglycemic for a large portion of their life despite constant depolarization of membrane, elevated cytoplasmic free Ca(2+) concentrations, and intact sensitivity of the exocytotic machinery to Ca(2+). A comparison of glucose- and meal-stimulated insulin secretion showed that, although Sur1 null mice do not secrete insulin in response to glucose, they secrete nearly normal amounts of insulin in response to feeding. Because Sur1 null mice lack an insulin secretory response to GLP-1, even though their islets exhibit a normal rise in cAMP by GLP-1, we tested their response to cholinergic stimulation. We found that perfused Sur1 null pancreata secreted insulin in response to the cholinergic agonist carbachol in a glucose-dependent manner. Together, these findings suggest that cholinergic stimulation is one of the mechanisms that compensate for the severely impaired response to glucose and GLP-1 brought on by the absence of Sur1, thereby allowing euglycemia to be maintained.

UI	MeSH Term	Description	Entries
D007328	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).	Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007515	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.	Islands of Langerhans,Islet Cells,Nesidioblasts,Pancreas, Endocrine,Pancreatic Islets,Cell, Islet,Cells, Islet,Endocrine Pancreas,Islet Cell,Islet, Pancreatic,Islets, Pancreatic,Langerhans Islands,Langerhans Islets,Nesidioblast,Pancreatic Islet
D008969	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.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010477	Perfusion	Treatment process involving the injection of fluid into an organ or tissue.	Perfusions
D011955	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.	Drug Receptors,Drug Receptor,Receptor, Drug
D011994	Recombinant Proteins	Proteins prepared by recombinant DNA technology.	Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D001786	Blood Glucose	Glucose in blood.	Blood Sugar,Glucose, Blood,Sugar, Blood
D002217	Carbachol	A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.	Carbamylcholine,Carbacholine,Carbamann,Carbamoylcholine,Carbastat,Carbocholine,Carboptic,Doryl,Isopto Carbachol,Jestryl,Miostat,Carbachol, Isopto
D003001	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.	Molecular Cloning
D004435	Eating	The consumption of edible substances.	Dietary Intake,Feed Intake,Food Intake,Macronutrient Intake,Micronutrient Intake,Nutrient Intake,Nutritional Intake,Ingestion,Dietary Intakes,Feed Intakes,Intake, Dietary,Intake, Feed,Intake, Food,Intake, Macronutrient,Intake, Micronutrient,Intake, Nutrient,Intake, Nutritional,Macronutrient Intakes,Micronutrient Intakes,Nutrient Intakes,Nutritional Intakes