STIMULUS-SECRETION COUPLING OF GLUCOSE-INDUCED INSULIN RELEASE - EFFECTS OF VALINOMYCIN UPON PANCREATIC-ISLET FUNCTION

In isolated rat pancreatic islets, valinomycin (0.01 to 1.0 μm) caused a dose-related facilitation of 86Rb+ outflow and a dose-related inhibition of the glucose-induced changes in both outflow and net uptake of 86Rb+. At high concentrations (0.1-1.0 μm), the ionophore also inhibited the oxidation of glucose and endogenous nutrients, decreased the adenylate charge, and lowered the concentration of reduced pyridine nucleotides in the islet cells. However, as little at 1.0 to 10.0 nm valinomycin caused anomalies in the handling of 45Ca2+ (suppression of the early inhibitory effect of glucose upon 45Ca2+ efflux, and reduction in the amount of 45Ca2+ recovered in the islets after an extensive washing procedure) and inhibition of insulin release. Moreover, when the effect of glucose upon K+ conductance was abolished by high concentrations of valinomycin (0.1-1.0 μm), the glucose-induced secondary rise in 45Ca2+ efflux was still observed. These findings suggest that the effects of glucose upon 86Rb+ and 45Ca2+ handling, respectively, although normally concomitant with one another, can be dissociated, in part at least, from one another. It is concluded that the glucose-induced reduction in K+ outflow may be unnecessary for the sugar to cause a partial remodeling of Ca2+ fluxes in the islet cells. © 1979.