title: Dual functional role of membrane depolarization/Ca2+ influx in rat pancreatic B-cell.
abstract: Transient exposure of rat pancreatic B-cell to 50 mM K+ ([K+50]) makes exocytosis unresponsive to further depolarization, i.e., stimulation with 100 mM K+ or 1 uM glyburide, which closes the ATP-sensitive K+ (K+ATP) channel, simultaneously with [K+50] does not produce any greater insulin secretion compared with [K+50] alone. In sharp contrast, 16.7 mM glucose ([G16.7]) applied simultaneously with [K+50] elicits an insulin response markedly greater than that produced by [K+50] alone, which is not attenuated by 100 uM diazoxide, an inhibitor of K+ATP channel closure. [G16.7]-induced insulin secretion at the basal K+ concn of 4.7 mM was greatly (93%) suppressed by 100 uM diazoxide. Insulin secretion induced by [K+50] plus [G16.7] ([K+50 + G16.7]) was markedly suppressed (70%) by 1 uM nifedipine, a Ca(2+)-channel blocker and was completely abolished by 2 mM 2-cyclohexen-1-one, which reportedly decreases reduced glutathione level and blocks glucokinase. This finding indicates that insulin release induced by [K+50 + G16.7] is not due to leakage produced by toxic stimuli but to activation of exocytosis. When graded concentrations (25 and 50 mM) of K+ were applied simultaneously with [G16.7] in the presence of 100 uM diazoxide, insulin response was clearly dependent on K+ concentration, indicating that the physiological range of membrane depolarization also activates the glucose-responsive effector. Membrane depolarization/Ca2+ influx directly stimulates hormone exocytosis on one hand and activates the K+ATP channel-independent glucose-responsive effector or effectors on the other in the B-cell. The nature of the glucose-responsive effector or effectors remains to be established.
authors.affiliation: Department of Geriatrics, Endocrinology and Metabolism, School of Medicine, Shinshu University, Nagano-ken, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Aizawa
authors.forename: M
authors.initials: M
authors.lastname: Komatsu
authors.forename: N
authors.initials: N
authors.lastname: Okada
authors.forename: T
authors.initials: T
authors.lastname: Yamada
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000493:pharmacokinetics*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002463:Cell Membrane Permeability / Q000502:physiology*; D003512:Cyclohexanones / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D005089:Exocytosis / Q000502:physiology; D005947:Glucose / Q000494:pharmacology; D007515:Islets of Langerhans / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000493:pharmacokinetics; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction / Q000502:physiology
chemical_list: D015220:Calcium Channels; D003512:Cyclohexanones; D015221:Potassium Channels; C028215:2-cyclohexen-1-one; D000255:Adenosine Triphosphate; D009543:Nifedipine; D005947:Glucose; D003981:Diazoxide; D011188:Potassium; D002118:Calcium