Kinetic and quantitative relationships between insulin release and 65Zn efflux from perifused islets

The kinetics of zinc release and insulin secretion were compared in perifused islets previously loaded for 24 h with 65Zn. In the absence of detectable insulin secretion, fractional basal 65Zn release was constant at 3-5%/h throughout the experimental periods, suggesting that basal efflux of zinc is primarily from a single extragranular compartment. Glucose (25 mM) alone caused a prompt release of both 65Zn and insulin. At low glucose concentrations, 3-isobutyl-1-methylxanthine (IBMX; 1 mM) did not affect either insulin or 65Zn efflux; however, the combination of glucose plus IBMX caused a large and parallel biphasic release of both 65Zn and insulin at ratios approximating 0.33. Similar results were obtained with glucose plus forskolin. Leucine (20 mM) plus IBMX caused a characteristic rapid secretion of insulin which waned with time. Efflux of 65Zn was also prompt; however, the ratio of secreted 65Zn to insulin gradually increased during stimulation from a near-theoretical value for cosecretion at the initial peak to 0.70 by the end of the stimulation. 65Zn efflux was sustained even after termination of the leucine plus IBMX stimulus