Intra-islet insulin suppresses glucagon release via GABA-GABAA receptor system
Intra-islet insulin suppresses glucagon release via GABA-GABAA receptor system
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DOI：
10.1016/j.cmet.2005.11.015
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发表时间：
2006-01-01
期刊：
影响因子：
29
通讯作者：
Wang, QH
中科院分区：
文献类型：
--
作者：
Xu, E;Kumar, M;Wang, QH
胰高血糖素的过度分泌是糖尿病高血糖发生的主要原因。胰高血糖素的分泌受到多种营养素的调节，其中葡萄糖是α细胞胰高血糖素分泌速率的主要决定因素。胰岛素的胰岛内作用对于发挥葡萄糖对α细胞的作用至关重要，因为在没有胰岛素的情况下，葡萄糖不能抑制体内胰高血糖素的释放。然而，胰岛素抑制细胞分泌胰高血糖素的确切机制尚不清楚。在这项研究中，我们发现胰岛素通过 Akt 激酶依赖性途径进行受体易位，从而诱导 α 细胞中 GABA(A) 受体的激活。这导致α细胞膜超极化，并最终抑制胰高血糖素分泌。我们认为该途径的缺陷会导致糖尿病高血糖。
Excessive secretion of glucagon is a major contributor to the development of diabetic hyperglycemia. Secretion of glucagon is regulated by various nutrients, with glucose being a primary determinant of the rate of alpha cell glucagon secretion. The intra-islet action of insulin is essential to exert the effect of glucose on the alpha cells since, in the absence of insulin, glucose is not able to suppress glucagon release in vivo. However, the precise mechanism by which insulin suppresses glucagon secretion from a cells is unknown. In this study, we show that insulin induces activation of GABA(A) receptors in the alpha cells by receptor translocation via an Akt kinase-dependent pathway. This leads to membrane hyperpolarization in the alpha cells and, ultimately, suppression of glucagon secretion. We propose that defects in this pathway(s) contribute to diabetic hyperglycemia.