Dual Functional Role of Membrane Depolarization/Ca2+ Influx in Rat Pancreatic B-Cell

Y Sato, T Aizawa, M Komatsu, N Okada, T Yamada - Diabetes, 1992 - Am Diabetes Assoc
Y Sato, T Aizawa, M Komatsu, N Okada, T Yamada
Diabetes, 1992Am Diabetes Assoc
Transient exposure of rat pancreatic B-cell to 50 mM K+ ([K+ 50]) makes exocytosis
unresponsive to further depolarization, ie, 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 …
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 Ca2+-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.
Am Diabetes Assoc