title: Metabolite-regulated ATP-sensitive K+ channel in human pancreatic islet cells.
abstract: 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+.
authors.affiliation: Department of Internal Medicine, Jewish Hospital, Washington University, St Louis, Missouri.
authors.forename: S
authors.initials: S
authors.lastname: Misler
authors.forename: W M
authors.initials: WM
authors.lastname: Gee
authors.forename: K D
authors.initials: KD
authors.lastname: Gillis
authors.forename: D W
authors.initials: DW
authors.lastname: Scharp
authors.forename: L C
authors.initials: LC
authors.lastname: Falke
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D003981:Diazoxide / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*
chemical_list: D015221:Potassium Channels; D000255:Adenosine Triphosphate; D005947:Glucose; D003981:Diazoxide