Metabolite-Regulated ATP-Sensitive K+ Channel in Human Pancreatic Islet Cells

• DOI: 10.2337/diab.38.4.422
• Publication Date: 2013-09-19T17:16:02Z
• Authors: Stanley Misler; William M Gee; Kevin D Gillis; David W Scharp; Lee C Falke
• Keywords: Secretagogue; Diazoxide; Tolbutamide; Pancreatic Islets

In patch-clamped surface cells of human islets, we identified an inwardly rectifying, voltage-independent K+ channel that may be a crucial link between substrate metabolism and depolarization-induced insulin secretion. It is the major open at rest. closes on exposure cell to secretagogue concentrations glucose or other metabolic fuels oral hypoglycemic sulfonylureas but reopens addition either inhibitor prevents utilization hyperglycemic sulfonamide diazoxide. Onset electrical activity coincides with closure by secretagogues. excised patches, this inhibited its cytoplasmic ATP. These results suggest in humans, as rodents, 1) rises ATP levels during trigger K+-channel depolarization 2) clinically useful sulfonamides modulate glucose-induced secretion, part affecting readily identifiable resting conductance pathway for K+.