Liu Zhenping, Jeppesen Per B, Gregersen Søren, Chen Xiaoping, Hermansen Kjeld
Department of Endocrinology and Metabolism C, Aarhus University Hospital, Aarhus Sygehus THG, Tage-Hansens Gade 2, DK-8000 Aarhus C, Denmark.
Rev Diabet Stud. 2008 Winter;5(4):232-44. doi: 10.1900/RDS.2008.5.232. Epub 2009 Feb 10.
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).
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.
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.
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.
葡萄糖和脂肪酸对β细胞功能的影响已得到充分证实，而关于氨基酸（AAs）的作用却知之甚少。
从NMRI小鼠分离的胰岛进行过夜培养。预孵育后，将分离的胰岛以及克隆的INS-1Eβ细胞在含有葡萄糖和氨基酸的改良Krebs-Ringer缓冲液中孵育60分钟。
在16.7 mmol/l（mM）葡萄糖浓度下，L-精氨酸、L-赖氨酸、L-丙氨酸、L-脯氨酸、L-亮氨酸和L-谷氨酰胺能剂量依赖性地增强葡萄糖刺激的胰岛素分泌，而DL-同型半胱氨酸则抑制胰岛素分泌。在20 mM L-脯氨酸、L-赖氨酸、L-丙氨酸、L-精氨酸时可获得最大胰岛素刺激效果（胰岛：增加2.5至6.7倍；INS-1E细胞：增加1.6至2.2倍）。仅在氨基酸浓度为20 mM时，L-谷氨酰胺和L-亮氨酸可增加葡萄糖刺激（16.7 mM）的胰岛素分泌（INS-1E细胞：分别增加1.5倍和1.3倍）。同型半胱氨酸在5.6 mM和16.7 mM葡萄糖浓度下均抑制胰岛素分泌。在1.1至25 mM的葡萄糖水平范围内，10 mM等摩尔浓度的L-脯氨酸、L-赖氨酸、L-精氨酸在所有应用的葡萄糖水平下均可增加小鼠胰岛和INS-1E细胞的胰岛素分泌，在25 mM葡萄糖时效果最佳。在10 mM浓度下，L-精氨酸和L-赖氨酸在所研究的氨基酸中具有最高的促胰岛素分泌能力。
L-精氨酸、L-赖氨酸、L-丙氨酸、L-脯氨酸、L-亮氨酸和L-谷氨酰胺以剂量和葡萄糖依赖性方式急性刺激小鼠胰岛和INS-1E细胞的胰岛素分泌，而DL-同型半胱氨酸则抑制胰岛素释放。
