The Role of Glucose, Glucagon and Glucocorticoids in the Regulation of Liver Glycogen Synthesis

Abstract

The conversion of liver glycogen synthetase b into a in vivo , induced by glucose or by glucocorticoids, is further enhanced when both treatments are combined. Once activated, the enzyme is rapidly inactivated by an injection of glucagon, epinephrine or cyclic AMP. When given together with glucose, these substances prevent the usual activation of the enzyme. The sensitivity of the mouse to glucagon was studied by the inactivation of liver glycogen synthetase and by the activation of liver phosphorylase; the first effect was obtained with lower doses than the second. On the other hand, about 100 times more glucagon was required to inactivate the synthetase previously activated by prednisolone than to prevent its activation by glucose. This difference in sensitivity can presumably not be explained by a different rate of destruction of cyclic AMP, as neither the total activity of the diesterase nor its affinity for the cyclic nucleotide is altered by the treatments. No evidence has been obtained suggesting that prednisolone lowers the sensitivity of the synthetase kinase towards cyclic AMP.