title: The role of ion channels in insulin secretion.
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 Ca2+. 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 Ca2+ levels ([Ca2+]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 Ca2+; VP also potentiates sustained insulin secretion by effects on depolarization. In contrast, inhibitors of insulin secretion decrease [Ca2+]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 alpha 1 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).
authors.affiliation: Division of Endocrinology, Metabolism, Diabetes, and Molecular Medicine, New England Medical Center, Boston, Massachusetts.
authors.forename: A E
authors.initials: AE
authors.lastname: Boyd
mesh_terms: D000818:Animals; D004594:Electrophysiology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007473:Ion Channels / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000494:pharmacology
chemical_list: D007328:Insulin; D007473:Ion Channels; D015221:Potassium Channels; D013453:Sulfonylurea Compounds; D005947:Glucose