On the mechanism by which glucocorticoids cause the activation of glycogen synthase in mouse and rat livers.
The administration of glucocorticoids to mice caused within 3 h an inactivation of glycogen phosphorylase and activation of glycogen synthase in their livers. In a Sephadex filtrate of liver extract, as well as in a purified glycogen fraction obtained from treated mice, but not in the same preparations obtained from control mice, glycogen synthase was activated without previous inactivation of phosphorylase. The initial rate of synthase activation in a Sephadex filtrate was proportional to the rate of glycogen synthesis in vivo in the same animal. When the glycogen fraction was isolated in the presence of soluble starch, it could be separated from phosphorylase, phosphorylase phosphatase and synthase phosphatase. When added to a control Sephadex filtrate, this purified glycogen fraction obtained from prednisolone-treated mice relieved synthase phosphatase from inhibition by phosphorylase a, indicating that it contained a transferable 'deinhibiting factor'. This deinhibiting factor appears to be a protein and was further purified by alkyl-Sepharose or DEAE-cellulose chromatography. Another modification introduced by treatment with prednisolone was that phosphorylase phosphatase was 1.5-2-fold more active than in the liver of control mice. This property however did not correlate with the rate of glycogen synthesis in vivo. Administration of actinomycin D prevented the expression of the glucocorticoid effects on the rate of glycogen synthesis in vivo and on the protein phosphatases in vitro. The deinhibition of synthase phosphatase was also observed in isolated rat hepatocytes incubated in the presence of glucocorticoids, but in these preparations synthase was not activated.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006006:Glycogen Synthase / Q000378:metabolism*; D006007:Glycogen-Synthase-D Phosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology*; D006005:Phosphorylases / Q000378:metabolism; D011239:Prednisolone / Q000494:pharmacology*; D051381:Rats
D011239:Prednisolone; D006005:Phosphorylases; D006006:Glycogen Synthase; D006007:Glycogen-Synthase-D Phosphatase