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 channel open at rest. It closes on exposure of the cell to secretagogue concentrations of glucose or other metabolic fuels and oral hypoglycemic sulfonylureas but reopens on addition of either a metabolic inhibitor that prevents substrate utilization or the hyperglycemic sulfonamide diazoxide. Onset of electrical activity coincides with channel closure by the secretagogues. In excised patches, the activity of this channel is inhibited at its cytoplasmic surface by ATP. These results suggest that in humans, as in rodents, 1) rises in cytoplasmic ATP levels during substrate metabolism trigger K+-channel closure and cell depolarization and 2) clinically useful sulfonamides modulate glucose-induced insulin secretion, in part by affecting a readily identifiable resting conductance pathway for K+.
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Original Articles|
April 01 1989
Metabolite-Regulated ATP-Sensitive K+ Channel in Human Pancreatic Islet Cells
Stanley Misler;
Stanley Misler
Departments of Internal Medicine (Jewish Hospital), Cell Biology/ Physiology, Electrical Engineering (Program in Biomedical Engineering), and Surgery, Washington University
St. Louis, Missouri
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William M Gee;
William M Gee
Departments of Internal Medicine (Jewish Hospital), Cell Biology/ Physiology, Electrical Engineering (Program in Biomedical Engineering), and Surgery, Washington University
St. Louis, Missouri
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Kevin D Gillis;
Kevin D Gillis
Departments of Internal Medicine (Jewish Hospital), Cell Biology/ Physiology, Electrical Engineering (Program in Biomedical Engineering), and Surgery, Washington University
St. Louis, Missouri
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David W Scharp;
David W Scharp
Departments of Internal Medicine (Jewish Hospital), Cell Biology/ Physiology, Electrical Engineering (Program in Biomedical Engineering), and Surgery, Washington University
St. Louis, Missouri
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Lee C Falke
Lee C Falke
Departments of Internal Medicine (Jewish Hospital), Cell Biology/ Physiology, Electrical Engineering (Program in Biomedical Engineering), and Surgery, Washington University
St. Louis, Missouri
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Address correspondence and reprint requests to Dr. Stanley Misler, Renal Division, The Jewish Hospital of St. Louis, 216 South Kingshighway Boulevard, St. Louis, MO 63110.
Diabetes 1989;38(4):422–427
Article history
Received:
September 01 1988
Revision Received:
October 21 1988
Accepted:
October 21 1988
Citation
Stanley Misler, William M Gee, Kevin D Gillis, David W Scharp, Lee C Falke; Metabolite-Regulated ATP-Sensitive K+ Channel in Human Pancreatic Islet Cells. Diabetes 1 April 1989; 38 (4): 422–427. https://doi.org/10.2337/diab.38.4.422
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