Metabolic, cationic and secretory response to D-glucose in depolarized andCa2+-deprived rat islets exposed to diazoxide

D-glucose stimulates insulin release from islets exposed to both diazoxide, to activate ATP-responsive K+ channels, and a high concentration of K+, to cause depolarization of the B-cell plasma membrane. Under these conditions , the insulinotropic action of D-glucose is claimed to occur despite unalte red cytosolic Ca2+ concentration, but no information is so far available on the changes in Ca2+ fluxes possibly caused by the hexose. In the present e xperiments, we investigated the effect of D-glucose upon Ca-45 efflux from islets exposed to both diazoxide and high K+ concentrations. In the presenc e of diazoxide and at normal extracellular Ca2+ concentration, D-glucose (1 6.7 mmol/l) inhibited insulin release at 5 mmol/l K+, but stimulated insuli n release at 90 mmol/l K+. In both cases, the hexose inhibited Ca-45 outflo w. In the presence of diazoxide, but absence of Ca2+, D-glucose (8.3 to 25. 0 mmol/l) first caused a rapid decrease in insulin output followed by a pro gressive increase in secretory rate. This phenomenon was observed both at 5 mmol/l or higher concentrations (30, 60 and 90 mmol/l) of extracellular K. it coincided with a monophasic decrease in Ca-45 efflux and either a tran sient (at 5 mmol/l K+) or sustained (at 90 mmol/l K+) decrease in overall c ytosolic Ca2+ concentration. The decrease in Ca-45 efflux could be due to i nhibition of Na+-Ca2+ countertransport with resulting localized Ca2+ accumu lation in the cell web of insulin-producing cells. A comparable process may be involved in the secretory response to D-glucose in islets exposed to di azoxide and a high concentration of K+ in the presence of extracellular Ca2 +. (C) 2000 Harcourt Publishers Ltd.