Intra-islet insulin suppresses glucagon release via GABA-GABA_A receptor system

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• 作者：Elaine Xu ; Mohan Kumar ; Yi Zhang ; William Ju ; Toshiyuki Obata ; Nina Zhang ; Shiying Liu ; Anna Wendt ; Shaoping Deng ; Yousuke Ebina ; Michael B. Wheeler ; Matthias Braun ; Qinghua Wang
• 关键词：CELLBIO ; SIGNALING ; HUMDISEASE
• 刊名：Cell Metabolism
• 出版年：2006
• 出版时间：January 2006
• 年：2006
• 卷：3
• 期：1
• 页码：47-58
• 全文大小：941 K

文摘

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 α cell glucagon secretion. The intra-islet action of insulin is essential to exert the effect of glucose on the α 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 α cells is unknown. In this study, we show that insulin induces activation of GABA_A receptors in the α cells by receptor translocation via an Akt kinase-dependent pathway. This leads to membrane hyperpolarization in the α cells and, ultimately, suppression of glucagon secretion. We propose that defects in this pathway(s) contribute to diabetic hyperglycemia.