Biomaterial Database

Na+ cotransport by metabolizable and nonmetabolizable amino acids stimulates a glucose-regulated insulin-secretory response. 1998

N H McClenaghan, and C R Barnett, and P R Flatt

School of Biomedical Sciences, University of Ulster, Coleraine, BT52 1SA, Northern Ireland. nhmcclenaghan@ulst.ac.uk

The involvement of Na+ in insulin-secretory responses to metabolizable and nonmetabolizable amino acids known to be cotransported with Na+, were examined using islet-derived BRIN-BD11 cells. At stimulatory (16.7 mM) glucose, 10 mM of l-alanine, alpha-aminoisobutyric acid (AIB) or l-proline stimulated 1.3- to 10. 4-fold (p < 0.01) insulin-secretory responses. In each case, these effects were significantly greater than those observed at nonstimulatory (1.1 mM) glucose (p < 0.01). While, tetrodotoxin blockade of voltage-dependent Na+ channels exerted no significant effect on insulin release, Na/K pump blockade with ouabain significantly promoted the amino acid-induced effects (p < 0.05). Replacement of extracellular Na+ with equimolar N-methyl-d-glucamine+ and omission of extracellular K+ or Ca2+ were all effective in removing the actions of each amino acid, confirming the critical role of ionic fluxes in the secretory responses to these amino acids. Collectively these results demonstrate that metabolizable and nonmetabolizable amino acids can induce glucose-dependent insulin-secretory responses by modulating electrogenic Na+ transport.

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
D008536	Meglumine	1-Deoxy-1-(methylamino)-D-glucitol. A derivative of sorbitol in which the hydroxyl group in position 1 is replaced by a methylamino group. Often used in conjunction with iodinated organic compounds as contrast medium.	Methylglucamine
D010042	Ouabain	A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like DIGITALIS. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-EXCHANGING ATPASE.	Acocantherin,G-Strophanthin,Acolongifloroside K,G Strophanthin
D011392	Proline	A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.	L-Proline,L Proline
D002118	Calcium	A basic element found in nearly all 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.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D005947	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.	Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D000078790	Insulin Secretion	Production and release of insulin from PANCREATIC BETA CELLS that primarily occurs in response to elevated BLOOD GLUCOSE levels.	Secretion, Insulin
D000254	Sodium-Potassium-Exchanging ATPase	An enzyme that catalyzes the active transport system of sodium and potassium ions across the cell wall. Sodium and potassium ions are closely coupled with membrane ATPase which undergoes phosphorylation and dephosphorylation, thereby providing energy for transport of these ions against concentration gradients.	ATPase, Sodium, Potassium,Adenosinetriphosphatase, Sodium, Potassium,Na(+)-K(+)-Exchanging ATPase,Na(+)-K(+)-Transporting ATPase,Potassium Pump,Sodium Pump,Sodium, Potassium ATPase,Sodium, Potassium Adenosinetriphosphatase,Sodium-Potassium Pump,Adenosine Triphosphatase, Sodium, Potassium,Na(+) K(+)-Transporting ATPase,Sodium, Potassium Adenosine Triphosphatase,ATPase Sodium, Potassium,ATPase, Sodium-Potassium-Exchanging,Adenosinetriphosphatase Sodium, Potassium,Pump, Potassium,Pump, Sodium,Pump, Sodium-Potassium,Sodium Potassium Exchanging ATPase,Sodium Potassium Pump