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Rev Diabet Stud, 2008, 5(4):232-244 DOI 10.1900/RDS.2008.5.232

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

Zhenping Liu1,2, Per B. Jeppesen1, Søren Gregersen1, Xiaoping Chen1, Kjeld Hermansen1

1Department of Endocrinology and Metabolism C, Aarhus University Hospital, Aarhus Sygehus THG, Tage-Hansens Gade 2, DK-8000 Aarhus C, Denmark
2The Second Affiliated Hospital of PLA General Hospital, Beijing 100091, P. R. China
Address correspondence to: Kjeld Hermansen, e-mail: kjeld.hermansen@dadlnet.dk

Manuscript submitted January 15, 2009; resubmitted February 16, 2009; accepted February 17, 2009.

Keywords: 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 glucose-stimulated insulin secretion dose-dependently, while DL-homocysteine inhibited insulin secretion. Maximal insulin stimulation was obtained at 20 mM L-proline, L-lysine, L-alanine, 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 L-lysine had the highest insulinotropic potency among the AAs investigated. CONCLUSION: L-arginine, L-lysine, L-alanine, 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 DL-homocysteine inhibits insulin release.

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