Inability of glucagon to regulate glycogen metabolism in rat hepatocytes isolated after fasting and refeeding high-carbohydrate diets.
Studies are described which demonstrate that the ability of glucagon, epinephrine, and dibutyryl-cAMP to stimulate glycogenolysis is impaired in rat hepatocytes isolated from animals starved for 24 h and then refed a sucrose-rich diet or refed standard rat chow. The impaired regulation of glycogenolysis by glucagon was observed within 24 h after refeeding and persisted for at least 3 days. The inability of glucagon to stimulate glycogen breakdown in the refed condition appeared to be due to a suppressed activation of glycogen phosphorylase and phosphorylase b kinase by the hormone. The capacity of glucagon to regulate pyruvate kinase and glycolysis was not altered by refeeding, suggesting that the defect lies beyond interaction of the hormone at its receptor. Prolonged incubation of hepatocytes from refed rats was accompanied by depletion of glycogen reserves and was accompanied by restoration of hormonal stimulation of glycogenolysis. Addition of glycogen to cell-free extracts was found to inhibit phosphorylase b kinase but not phosphorylase. The findings of this investigation are consistent with the interpretation that high levels of glycogen present of liver after refeeding may lead to a diminished activity of phosphorylase b kinase and its hormonal regulation.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D004040:Dietary Carbohydrates / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D005215:Fasting; D005934:Glucagon / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D010764:Phosphorylase Kinase / Q000378:metabolism; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats
D004040:Dietary Carbohydrates; D008112:Liver Glycogen; D000001:Calcimycin; D003994:Bucladesine; D005934:Glucagon; D006005:Phosphorylases; D010764:Phosphorylase Kinase; D004837:Epinephrine