Dose- and Glucose-Dependent Effects of Amino Acids on Insulin Secretion from Isolated Mouse Islets and Clonal INS-1E Beta-Cells


  • Zhenping Liu, Per B. Jeppesen , Søren Gregersen , Xiaoping Chen, Kjeld Hermansen Department of Endocrinology and Metabolism C, Aarhus University Hospital, Aarhus Sygehus THG, Tage-Hansens Gade 2, DK-8000 Aarhus C, Denmark


diabetes · INS-1E beta-cells · amino acid · glucose · insulin secretion


BACKGROUND: The influence of glucose and fatty acids on beta-cell function is well established whereas little is known about the role of amino acids (AAs). METHODS: Islets isolated from NMRI mice were incubated overnight. After preincubation, isolated islets as well as clonal INS-1E beta-cells were incubated for 60 min in a modified Krebs Ringer buffer containing glucose and AAs. RESULTS: At 16.7 mmol/l (mM) glucose, L-arginine, L-lysine, L-alanine, L-proline, L-leucine, and L-glutamine potentiated glucosestimulated insulin secretion dose-dependently, while DLhomocysteine inhibited insulin secretion. Maximal insulin stimulation was obtained at 20 mM L-proline, L-lysine, Lalanine, L-arginine (islets: 2.5 to 6.7 fold increase; INS-1E cells: 1.6 to 2.2 fold increase). L-glutamine and L-leucine only increased glucose-stimulated (16.7 mM) insulin secretion (INS-1E cells: 1.5 and 1.3 fold, respectively) at an AA concentration of 20 mM. Homocysteine inhibited insulin secretion both at 5.6 mM and 16.7 mM glucose. At glucose levels ranging from 1.1 to 25 mM, the equimolar concentration of 10 mM, L-proline, L-lysine, L-arginine increased insulin secretion from mouse islets and INS-1E cells at all glucose levels applied, with a maximal effect obtained at 25 mM glucose. At a concentration of 10 mM, L-arginine and Llysine had the highest insulinotropic potency among the AAs investigated. CONCLUSION: L-arginine, L-lysine, Lalanine, L-proline, L-leucine and L-glutamine acutely stimulate insulin secretion from mouse islets and INS-1E cells in a dose- and glucose-dependent manner, whereas DLhomocysteine inhibits insulin release.