Responsiveness of glycogen breakdown to cyclic AMP in perfused liver from rats with insulin-induced hypoglycemia.

M Vardanega-Peicher,R Curi,K.F Nascimento,R.B Bazotte,S Pagliarini E Silva

doi:10.1590/s0100-879x2003000100007

Abstract

The responsiveness of glycogen breakdown to cAMP was investigated in isolated perfused liver from male Wistar fed rats (200-220 g) with insulin-induced hypoglycemia. The activation of glycogenolysis by 3 microM cAMP was decreased (P<0.05) in livers from rats with hypoglycemia induced by the administration of insulin or during the direct infusion of insulin into the isolated liver. The direct effect of insulin on glycogen catabolism promoted by 3 microM cAMP occurred as early as 3 min after starting insulin infusion. In contrast, the cAMP agonists resistant to phosphodiesterases, 8Br-cAMP and 6MB-cAMP, used at the same concentration as cAMP, i.e., 3 microM, did not modify the effect of insulin. The data suggest that the decreased hepatic responsiveness of glycogen breakdown during insulin-induced hypoglycemia is a direct effect of insulin decreasing the intracellular levels of cAMP.

Highlights

During insulin-induced hypoglycemia, hepatic glucose production must increase to match the energy demands of the brain
Because the activation of hepatic glycogenolysis promoted by ß-adrenergic agonists is mediated by adenosine-3'-5'-cyclic monophosphate, we decided to investigate the participation of cAMP in this effect [6]
Hepatic glycogen breakdown in the liver is regulated in an opposite manner by insulin and cAMP-elevating agents

Summary

Introduction

During insulin-induced hypoglycemia, hepatic glucose production must increase to match the energy demands of the brain. In the fed state, when liver glycogen stores are present, the hepatic response to insulininduced hypoglycemia operates primarily through glycogenolysis [1,2] rather than gluconeogenesis [3]. We demonstrated [6] that the administration of insulin at pharmacological levels was capable of inhibiting isoproterenol-induced hepatic glycogen breakdown. Because the activation of hepatic glycogenolysis promoted by ß-adrenergic agonists is mediated by adenosine-3'-5'-cyclic monophosphate (cAMP), we decided to investigate the participation of cAMP in this effect [6]. Since the cellular levels of cAMP and analogues are proportional to the extracellular concentration used in the liver perfusion experiments [7], it is possible to investigate the hepatic responsiveness of glycogen break-

Methods

Results

Conclusion