Adenosine 3′,5′-Monophosphate-Dependent and -Independent Inhibitory Effects of Epinephrine on Insulin Release in Rat Pancreatic Islets

The role of cAMP in the inhibitory effect of epinephrine on insulin secretion was studied by comparing the dose-response relationships of the effects of epinephrine on insulin release and [³H]cAMP content in rat pancreatic islets prelabeled with [2-³H]adenine and stimulated by various agents in vitro.

Glucagon-stimulated insulin release and increased [³H]cAMP in islets were inhibited in a parallel dosedependent fashion by epinephrine. In contrast, glucosestimulated insulin release was more sensitve to inhibition by epinephrine than was glucose-induced [³H]- cAMP accumulation. Thus, 3 × 10^-8 M epinephrine produced 50% inhibition of the insulin release stimulated by 26.7 tnM glucose, whereas 10^-6 M epinephrine was required to produce 50% inhibition of the [³H]cAMP response to glucose. In contrast to the inhibitory effects of a high concentration of epinephrine (10^-6 M) on glucagon and glucose-stimulated increases in islet [³H]cAMP, this concentration of epinephrine did not decrease the increased [³H]cAMP levels in islets incubated with either the phosphodiesterase inhibitor, 3- isobutyl-1-methylxanthine (IBMX, 1.0 mM) or the adenylate cyclase stimulator, cholera toxin (10 μg/ml). Phentolamine (10^-5 M) abolished the inhibitory effects of 10^-6 M epinephrine on both the [³H]cAMP and the insulin response to glucose.

The data suggest that epinephrine inhibits glucoseinduced insulin release by a dual α-adrenergic action: 1) at low concentrations, epinephrine may inhibit insulin release by a mechanism (s) distinct from the adenylate cyclase-cAMP system; and 2) at high concentrations, epinephrine may further inhibit insulin release by interfering with the ability of glucose to increase cAMP in the pancreatic B cell rather than by any direct effect on adenylate cyclase. (Endocrinology102: 1733, 1978)