Fasting enhances glycogen synthase activation in hepatocytes from insulin-resistant genetically obese (fa/fa) rats.
Glycogen synthase activation and phosphorylase inactivation by glucose were studied in hepatocytes isolated from fed or overnight-fasted lean or genetically obese (fa/fa) rats. In cells from fed animals, both the time course and dose-response to glucose of synthase activation were the same in both groups, despite higher levels of phosphorylase a in hepatocytes from obese animals. In contrast, in cells from fasted obese animals synthase activation with or without glucose was enhanced severalfold over that of lean controls, despite similar levels of phosphorylase a and of total (a + b) synthase activities. In both nutritional conditions glucose 6-phosphate concentrations were 2-3-fold higher in obese-rat hepatocytes than in lean-rat cells. In addition, synthase activation was transient in the fasted lean group, but was sustained in obese-rat hepatocytes. The rate of synthase activation was, however, comparable in lean- and obese-rat liver Sephadex G-25 filtrates, irrespective of the nutritional state of the donor rats. It is concluded that enhanced synthase activation in hepatocytes from starved obese rats might be due to an unbalanced synthase interconversion brought about by elevated glucose 6-phosphate concentrations and impaired kinase [van de Werve & Massillon (1990) Biochem. J. 269, 795-799], rather than to an intrinsic change in synthase phosphatase.
van de Werve
G
G
Department of Nutrition, Faculty of Medicine, University of Montreal, Quebec, Canada.
D000818:Animals; D003911:Dextrans; D004351:Drug Resistance; D004789:Enzyme Activation; D005215:Fasting / Q000378:metabolism*; D005260:Female; D005374:Filtration; D005947:Glucose / Q000378:metabolism; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D010762:Phosphorylase a / Q000378:metabolism; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014532:Uridine Diphosphate Glucose / Q000378:metabolism
D003911:Dextrans; D005958:Glucosephosphates; D007328:Insulin; D019298:Glucose-6-Phosphate; C025614:sephadex; D010762:Phosphorylase a; D006005:Phosphorylases; D006006:Glycogen Synthase; D005947:Glucose; D014532:Uridine Diphosphate Glucose