The role of ion channels in insulin secretion

✍ Scribed by A. E. Boyd III

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 810 KB
• Volume: 48
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240480303

✦ Synopsis

Abstract

Ion channels in beta cells regulate electrical and secretory activity in response to metabolic, pharmacologic, or neural signals by controlling the permeability to K^+^ and Ca^2+^. The ATP‐sensitive K^+^ channels act as a switch that responds to fuel secretagogues or sulfonylureas to initiate depolarization. This depolarization opens voltage‐dependent calcium channels (VDCC) to increase the amplitude of free cytosolic Ca^2+^ levels ([Ca^2+^]i), which triggers exocytosis. Acetyl choline and vasopressin (VP) both potentiate the acute effects of glucose on insulin secretion by generating inositol 1,4,5‐trisphosphate to release intracellular Ca^2+^; VP also potentiates sustained insulin secretion by effects on depolarization. In contrast, inhibitors of insulin secretion decrease [Ca^2+^]i by either hyperpolarizing the beta cell or by receptor‐mediated, G‐protein‐coupled effects to decrease VDCC activity. Repolarization is initiated by voltage‐ and Ca^2+^‐activated K^+^ channels. A human insulinoma voltage‐dependent K^+^ channel cDNA was recently cloned and two types of alpha1 subunits of the VDCC have been identified in insulin‐secreting cell lines. Determining how ion channels regulate insulin secretion in normal and diabetic beta cells should provide pathophysiologic insight into the beta cell signal transduction defect characteristic of non‐insulin dependent diabetes (NIDDM).