Alpha 2-adrenergic Inhibition of Insulin Secretion Via Interference with Cyclic AMP Generation in Rat Pancreatic Islets

Glucose-induced secretion and cyclic AMP accumulation in isolated rat pancreatic islets as well as GTP-activated adenylate cyclase of the membrane-rich preparation from the islets were strongly inhibited by some alpha-adrenergic agonists. The relative potencies of the agonists, estimated according to their dose-dependent actions, were in such an order that clonidine greater than epinephrine (congruent to norepinephrine) greater than phenylephrine congruent to methoxamine, regardless of which of the three parameters (i.e., insulin release, cyclic AMP accumulation, and adenylate cyclase activity) was used for estimation. There was a highly significant correlation between the amounts of cyclic AMP accumulation and the rate of insulin release that were changed in response to these agonists. The order of the potencies of alpha-adrenergic antagonists to reverse epinephrine inhibition of these parameters was invariably yohimbine congruent to dihydroergotamine congruent to phenylephrine greater than prazosin. In conclusion, the rat islet cell membrane is equipped with alpha 2-adrenoceptors which are linked to adenylate cyclase to cause diminution of the cellular content of cyclic AMP; insulin secretion may be inhibited consequently.