Effects of glucocorticoids and insulin on 3',5'-AMP phosphodiesterase activity in adrenalectomized rats.

Abstract

Glucocorticoids stimulate the rate of lipolysis which is reduced in adrenalectomized animals. This hormonal action is antagonized by insulin. The antilipolytic action of insulin appears to be mediated by a reduced intracellular concentration of 3′,5′-AMP. This reduction can partly be attributed to an insulin-induced acceleration of 3′,5′-AMP degradation. — It is shown that the stimulatory influence of glucocorticoids on lipolysis is due to a reduction of 3′,5′-AMP phosphodiesterase (PDE) activity, which is increased by adrenalectomy. PDE activity was also increased in liver, skeletal muscle and kidney of adrenalectomized rats; treatment with a glucoeorticoid prevented this increase.In vitro, PDE purified from beef heart was inhibited by glucocorticoids in high concentrations (Ki=1.1 · 10−3 M for 6 α-methylprednisolone hemisuccinate,K i=1.6 · 10−3 M for prednisolone succinate).In vivo, the glucocorticoid-induced decrease of PDE activity (with retarded onset as shown in liver), may essentially be attributed to a decreased enzyme synthesis. — Studies on the interaction of insulin and glucocorticoids on PDE activity were performed in the liver. In adrenalectomized, alloxan diabetic rats insulin stimulated PDE activity suppressed by treatment with a glucoeorticoid, unsuppressed PDE activity was not increased by insulin. In contrast, the action of glucocorticoids on PDE activity was independent of the presence or the effectiveness of insulin.