Ashcroft F M, Harrison D E, Ashcroft S J
Nature. 1984;312(5993):446-8. doi: 10.1038/312446a0.
The major physiological stimulus for the secretion of insulin from the pancreatic beta-cell is an increase in the plasma glucose concentration. It is well established that glucose-stimulated insulin secretion is associated with the appearance of electrical activity in the beta-cell; glucose concentrations above the threshold level for insulin release produce a slow membrane depolarization followed by either oscillatory bursts of action potentials (5-15 mM glucose) or continuous spiking (greater than 16 mM glucose). Tracer flux studies and microelectrode measurements using intact islets of Langerhans have indicated that the initial depolarization induced by glucose is caused by a decrease in the resting membrane permeability to potassium. Evidence also suggests that the electrical, ionic and secretory responses to glucose are mediated by the metabolism of the sugar within the beta-cell. By using cell-attached membrane patches from isolated rat pancreatic beta-cells, we have now identified a potassium channel (G-channel) that is active at the resting potential and is inhibited by glucose. Closure of this channel requires glucose metabolism. This is the first report of a potassium channel whose activity is modulated by glucose, and which may couple metabolic and ionic events involved in the secretion of insulin.
胰腺β细胞分泌胰岛素的主要生理刺激因素是血浆葡萄糖浓度的升高。葡萄糖刺激的胰岛素分泌与β细胞电活动的出现有关，这一点已得到充分证实；高于胰岛素释放阈值水平的葡萄糖浓度会导致细胞膜缓慢去极化，随后出现动作电位的振荡爆发（葡萄糖浓度为5 - 15 mM）或持续发放（葡萄糖浓度大于16 mM）。使用完整胰岛进行的示踪剂通量研究和微电极测量表明，葡萄糖诱导的初始去极化是由静息膜对钾离子的通透性降低所致。有证据还表明，对葡萄糖的电、离子和分泌反应是由β细胞内糖的代谢介导的。通过使用从分离的大鼠胰腺β细胞获得的细胞贴附膜片，我们现已鉴定出一种钾通道（G通道），该通道在静息电位时处于激活状态，并受到葡萄糖的抑制。该通道的关闭需要葡萄糖代谢。这是关于一种钾通道的首次报道，其活性受葡萄糖调节，且可能将胰岛素分泌过程中涉及的代谢和离子事件联系起来。
