Zhang S, Kim K H
Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907, USA.
J Endocrinol. 1995 Oct;147(1):33-41. doi: 10.1677/joe.0.1470033.
Malonyl-CoA, which is the unique product of acetyl-CoA carboxylase (ACC), may serve as a metabolic coupler in glucose-stimulated insulin secretion by pancreatic beta-cells. Therefore we examined if and how ACC is affected by glucose in association with insulin secretion. Glucose induces a rapid increase in ACC activity which is closely related to insulin secretion in a dose- and time-dependent manner. The acute effect of glucose in increasing ACC activity is caused by dephosphorylation of existing ACC molecules, without the production of new enzyme. Inhibition of ACC dephosphorylation and activation by the use of okadaic acid led to diminished glucose-mediated insulin secretion. Likewise, when ACC phosphorylation and inactivation were induced by the use of 5-amino 4-imidazole-carboxamide ribotide, an AMP analog and activator of 5'-AMP protein kinase, the glucose-induced insulin secretion was virtually nil. In the long term, glucose induced ACC and increased insulin secretion. In beta-cells, ACC gene expression is controlled by promoter II and glucose activated promoter II expression. ACC promoter I is not expressed in beta-cells. Maximum activation of ACC and insulin secretion by glucose in the short term occurred at 5 mM glucose. On the other hand, activation of the expression of ACC promoter II occurred when the cells were exposed to high glucose concentrations for a long period of time. Thus, we have shown that ACC, the only enzyme that produces malonyl-CoA, is activated by glucose; activation of ACC is accomplished by dephosphorylation in the short term and by induction of ACC by gene activation in the long term.
丙二酰辅酶A是乙酰辅酶A羧化酶（ACC）的唯一产物，它可能作为胰腺β细胞葡萄糖刺激胰岛素分泌过程中的代谢偶联物。因此，我们研究了ACC是否以及如何受到与胰岛素分泌相关的葡萄糖的影响。葡萄糖以剂量和时间依赖性方式诱导ACC活性迅速增加，这与胰岛素分泌密切相关。葡萄糖增加ACC活性的急性效应是由现有ACC分子的去磷酸化引起的，而不是新酶的产生。使用冈田酸抑制ACC去磷酸化和激活会导致葡萄糖介导的胰岛素分泌减少。同样，当使用5-氨基-4-咪唑甲酰胺核糖核苷酸（一种AMP类似物和5'-AMP蛋白激酶的激活剂）诱导ACC磷酸化和失活时，葡萄糖诱导的胰岛素分泌几乎为零。长期来看，葡萄糖诱导ACC并增加胰岛素分泌。在β细胞中，ACC基因表达受启动子II控制，葡萄糖激活启动子II的表达。ACC启动子I在β细胞中不表达。短期内，葡萄糖对ACC和胰岛素分泌的最大激活发生在5 mM葡萄糖浓度时。另一方面，当细胞长时间暴露于高葡萄糖浓度时，ACC启动子II的表达被激活。因此，我们已经表明，产生丙二酰辅酶A的唯一酶ACC被葡萄糖激活；ACC的激活在短期内通过去磷酸化实现，在长期内通过基因激活诱导ACC来完成。
