Mechanism of Control of Hepatic Glycogenesis by Insulin

Abstract

Insulin produces an increase in the conversion of the D form (glucose-6-P dependent) of liver glycogen synthase to the I form (glucose-6-P independent) when injected intravenously into fed alloxan diabetic rats. Insulin activates glycogen synthase previously inactivated by glucagon in isolated perfused livers from normal rats, while increasing [14C]glucose incorporation into glycogen and decreasing glucagon-stimulated glucose production. This change in synthase activity is associated with a decrease in synthase (protein) kinase activity and tissue adenosine 3′,5′-monophosphate levels when insulin is used to antagonize the effects of glucagon. Finally, insulin alone has a direct effect on the activation of glycogen synthase (D to I shift) in perfused livers from normal rats if insulin infusion is begun after an initial 30-min perfusion period. This effect is maximal between 6 and 15 min and is no longer present after 30 min. Associated changes include an increase in [14C]-glucose incorporation into glycogen at 10 min and a decrease in synthase kinase activity at 6 and 15 min. This decrease in kinase activity is not associated with a decrease in apparent hepatic concentrations of adenosine 3′,5′-monophosphate.