Verapamil- and Cadmium-Resistant Stimulation of Calcium Uptake and Insulin Release by d-Glucose in Depolarised Pancreatic Islets Exposed to Diazoxide

Abstract

The possible activation by d-glucose of voltage-insensitive Ca 2+ channels in rat pancreatic islets was investigated by measuring the release of insulin, as well as the net uptake and efflux of 45Ca, in islets incubated in the presence of 30 mM K +, 0.25 mM diazoxide and either 0.05 mM verapamil or 0.04 mM Cd 2+. In the presence of verapamil, d-glucose (16.7 mM) stimulated, over 90-min incubation, both 45Ca net uptake and insulin release. Likewise, in prelabelled perifused islets, a rise in d-glucose concentration from 2.8 to 16.7 mM augmented both 45Ca outflow and insulin output. When the concentration of the hexose was raised from zero to 8.3 mM, in which case the glucose-induced stimulation of Ca 2+ influx is thought to occur mainly at the intervention of voltage-insensitive Ca 2+ channels, and when Cd 2+ was used to selectively block L-type Ca 2+ channels, a stimulation of both 45Ca efflux and insulin release was again observed in islets perifused, at high extracellular K + concentration, in the presence of diazoxide. These findings support the view that, in depolarised islets in which the ATP-sensitive K + channels are fully activated by diazoxide, the stimulation of insulin release by d-glucose might involve the gating of voltage-insensitive Ca 2+ channels.