Response of liver glycogen synthase and phosphorylase to in vivo glucose and glucose analogues

Abstract

Glucose causes a rapid increase in the proportion (%) of glycogen synthase in the active (I) form and a rapid decrease in the proportion of phosphorylase in the active (a) form in both fed and fasted rats. The changes in synthase I and phosphorylase a are more rapid in fasted animals. With graded doses of glucose, the maximal decrease in phosphorylase a occurred at a dose that was considerably smaller than that required to maximally stimulate an increase in % synthase I. Thus, in the intact animal a dissociation between the effects of glucose on the synthase and phosphorylase systems was observed. Sorbitol, mannose, galactose, and arabinose all stimulated an increase in synthase I but did not significantly affect the proportion of phosphorylase in the a form. The % synthase I was not significantly affected by a number of other glucose homologues, pentoses, or three-carbon gluconeogenic substrates. The ketoses fructose and mannoheptulose both caused a striking increase in % phosphorylase a and a decrease in % synthase I, i.e., results opposite to those of glucose. The mechanism by which fructose induces these changes is not known, but the mannoheptulose effects may be accounted for by a rise in liver cAMP concentration.

Glucose Toxicity Is Responsible for the Development of Impaired Regulation of Endogenous Glucose Production and Hepatic Glucokinase in Zucker Diabetic Fatty Rats

“…Improved hepatic glycogen synthesis in response to elevated plasma glucose. The response of the liver to a glucose load involves the sequential inactivation of glycogen phosphorylase and activation of glycogen synthase in most (52)(53)(54) but not all (55) studies. A major part of the glucose taken up by the liver is normally stored as glycogen (56).…”

Glucose has to be phosphorylated to activate glycogen synthase, but not to inactivate glycogen phosphorylase in hepatocytes

“…3-0-Methylglucose is unable to interact with glycogen phosphorylase and, indeed, a lack of effect of 3-O-methy!g!uco~ on liver phosphorylase a-to-b conversion has been reported using purified enzyme [3] and also in. in vivo experiments [14].…”

Chronic suppression of insulin by diazoxide alters the activities of key enzymes regulating hepatic gluconeogenesis in Zucker rats

“…Glycogen phosphorylase a assay The GPa activity was assayed in the direction of glycogen synthesis as described by Nuttall et al (34). The assay was conducted at 30 8C and initiated by adding a reaction mixture containing 2[N-morpholino]ethanesulfonic acid (pH 6.3), glucose-1-phosphate, caffeine, glycogen and 14 C-labeled glucose-1-phosphate diluted hepatic tissue extract.…”