Effects of epinephrine and the cyclic AMP phosphodiesterase inhibitor SQ 20009 on glucose and glycogen metabolism in skeletal muscle

Abstract

In rat diaphragm incubated in vitro, epinephrine and isoproterenol inhibited glucose uptake and the incorporation of radioactive glucose into glycogen. The metabolic effects of epinephrine were inhibited by the beta-adrenergic blocking agents, propranolol and sotalol, but not by the alpha-adrenergic blocking drug, phentolamine. The phosphodiesterase inhibitor, 1-ethyl-4-(isopropylidine-hydrazino)-1H-pyrazolo-(3,4-b)-pyridine-5-carboxylic acid, ethyl ester, hydrochloride (SQ 20009), also decreased glucose uptake and glycogen synthesis. In contrast to the action of epinephrine, exogenous calcium ions were required for the effects of SQ 20009 on phosphorylase activation, increased tissue glucose- 6-phosphate levels and lactate production. It was concluded that the inhibition of glucose uptake that occurred when tissue cyclic AMP levels were increased by beta-adrenergic drugs or phosphodiesterase inhibitors was not due directly to accumulation of glucose-6-phosphate from glycogenolysis but was a result of a cyclic AMP-mediated inhibition of glycogen synthesis.