Zhang S, Kim K H
Department of Biochemistry, Purdue University, West Lafayette, Indiana, 47907, USA.
Biochem Biophys Res Commun. 1996 Dec 24;229(3):701-5. doi: 10.1006/bbrc.1996.1868.
In pancreatic beta-cells, stimulation of insulin secretion by glucose and other nutrients requires metabolism of these nutrients to acetyl-CoA. Circumstantial evidence suggests that the conversion of acetyl-CoA to malonyl-CoA, which is a powerful inhibitor for carnitine palmitoyltransferase 1 and fatty acid oxidation, leads to insulin exocytosis, presumably by fatty acyl-CoA activation of certain ion channels. Since acetyl-CoA carboxylase (ACC) is the only enzyme which synthesizes malonyl-CoA, we generated transfectants of INS-1 cells which express antisense ACC mRNA in order to unequivocally establish that ACC is involved in glucose-induced insulin secretion. These cells showed lower ACC mRNA, protein and enzymatic activity than those of the control cells. Insulin secretion induced by nutrients such as glucose, amino acids, ketoisocaproate, and fatty acids was diminished commensurate with the level of ACC, while KCl induced insulin secretion was not affected.
在胰腺β细胞中，葡萄糖和其他营养物质对胰岛素分泌的刺激需要这些营养物质代谢生成乙酰辅酶A。间接证据表明，乙酰辅酶A转化为丙二酰辅酶A（一种对肉碱棕榈酰转移酶1和脂肪酸氧化有强大抑制作用的物质）会导致胰岛素胞吐，推测是通过某些离子通道的脂酰辅酶A激活来实现的。由于乙酰辅酶A羧化酶（ACC）是唯一合成丙二酰辅酶A的酶，我们构建了INS-1细胞转染体，其表达反义ACC mRNA，以便明确确定ACC参与葡萄糖诱导的胰岛素分泌。这些细胞的ACC mRNA、蛋白质和酶活性均低于对照细胞。由葡萄糖、氨基酸、酮异己酸和脂肪酸等营养物质诱导的胰岛素分泌与ACC水平相应降低，而氯化钾诱导的胰岛素分泌不受影响。
