Regulation of glucagons secretion at low glucose concentrations: Evidence for adenosine triphosphate-sensitive potassium channel involvement (Endocrinology, 2005, 146:5514-5521)

報告日期: 2006/04/21
報告時間: 16:00/16:50
報告學生: 王雅貞
講評老師: 鄭瑞棠


Regulation of Glucagon Secretion at Low Glucose

Concentrations: Evidence for Adenosine Triphosphate-

Sensitive Potassium Channel Involvement


Speaker:王雅貞                                                                      602  pm 4:00




The release of glucagon is stimulated by hypoglycemia and inhibited by hyperglycemia, insulin, and somatostatin. Glucagon is a potent counterregulatory hormone that opposes the action of insulin in controlling glycemia. The cellular mechanisms by which pancreatic a-cell glucagon secretion occurs in response to insulin-induced hypoglycemia are poorly known. SUR1/KIR6.2-type ATP-sensitive potassium (KATP) channels are known to play a role in regulation of insulin release, but their role in glucagon secretion is less clear. In this study, authors examined hypoglycemia-induced glucagon secretion in vitro in isolated islets and in vivo using Sur1KO mice lacking neuroendocrine-type KATP channels and paired wild-type (WT) controls. Sur1KO mice fed ad libitum have normal glucagon levels and mobilize hepatic glycogen in response to exogenous glucagon but exhibit a blunted glucagon response to insulin-induced hypoglycemia. Glucagon release from Sur1KO and WT islets is increased at low glucose concentractions and suppressed by increasing glucose concentrations. WT islets increase glucagon secretion approximately 20-fold when challenged with low glucose vs. approximately 2.7-fold for Sur1KO islets. Glucagon release requires Ca2+ and is inhibited by nifedipine. Consistent with a regulatory interaction between KATP channels and intra-islet zinc-insulin, WT islets exhibit an inverse correlation between b-cell secretion and glucagon release. Glibenclamide stimulated insulin secretion and reduced glucagon release in WT islets but was without effect on secretion from Sur1KO islets. The results indicate that pancreatic islets can sense and respond directly to changes in ambient glucose and mount a counterregulatory response in vitro, secreting glucagon in response to hypoglycemia, independent of CNS regulation. Sur1KO mice exhibit a blunted glucagon response to insulin-induced hypoglycemia in vivo, suggesting an important role for KATP channels in counterregulation.



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