Epinephrine modifications of insulin release and of 86Rb+ or 45Ca2+ fluxes in rat islets.

The effects of epinephrine on insulin release, 86Rb+ fluxes, and 45Ca2+ fluxes were measured in rat islets. In the presence of 10 mM glucose, epinephrine did not affect 86Rb+ influx and slightly increased net uptake. It caused a monophasic inhibition of release and a biphasic decrease in 86Rb+ efflux. A maximum effect was observed with 1 microM epinephrine, but release was more markedly inhibited by lower concentrations of the catecholamine than was the efflux. Epinephrine inhibition of release and efflux was reversed by phentolamine and yohimbine but not by prazosin or propranolol. It was mimicked by norepinephrine and clonidine. The inhibition of 86Rb+ efflux persisted when insulin release was prevented by omission of extracellular calcium. Ouabain or high K+ markedly increased 86Rb+ efflux in the presence of glucose and epinephrine; theophylline and quinine had a similar but smaller effect. None of these agents restored insulin release. Epinephrine abolished the insulinotropic effect of arginine without altering the rise in 86Rb+ efflux triggered by the amino acid. Epinephrine abolished insulin release but inhibited 45Ca2+ efflux only partially during stimulation by glucose or by barium plus theophylline. The results show that epinephrine does not inhibit insulin release by activating the Na pump or by increasing K permeability of the B cell membrane. On the contrary, the inhibition of release is accompanied by a decrease in 86Rb+ efflux. Both result from activation of alpha 2-receptors but are not causally related; they could be due to remodeling of Ca2+ fluxes and/or changes in cAMP levels.