Increased synthase phosphatase activity is responsible for the super-activation of glycogen synthase in hepatocytes from fasted obese Zucker rats.
Addition of 60 mM glucose caused a similar partial activation of glycogen synthase in hepatocytes isolated from overnight fasted Wistar rats and from fasted lean Zucker (Fa/fa?) rats. In contrast, the activation went rapidly to completion in cells from fasted obese (fa/fa) rats. Subsequent addition of 4 microM microcystin, a potent inhibitor of type 1 and type 2A protein phosphatases, induced a rapid inactivation of glycogen synthase, which occurred at a similar rate in all three types of hepatocytes. This suggests that the super-activation of glycogen synthase in hepatocytes from fasted obese rats is not due to a lower synthase kinase activity. Glycogen synthase phosphatase was quantitatively assayed in broken-cell preparations from the same livers, with exogenous synthase b as substrate. The synthase phosphatase activity in the fa/fa livers was 3-fold higher than that in the livers from both lean Zucker rats and Wistar rats. This difference has to be attributed to an increased synthase phosphatase activity of the glycogen-bound protein phosphatase-1 in livers of fasted obese rats. The results suggest that in the latter animals the available insulin exceeds the insulin resistance of the liver. The resulting overexpression of the insulin-dependent synthase-phosphatase-1G activity may explain the super-activation of glycogen synthase in response to a glucose challenge.
Lavoie
L
L
Department of Nutrition, Faculty of Medicine, University of Montreal, Quebec, Canada.
Bollen
M
M
Stalmans
W
W
van de Werve
G
G
D000818:Animals; D004789:Enzyme Activation; D005215:Fasting; D005947:Glucose / Q000494:pharmacology; D006006:Glycogen Synthase / Q000378:metabolism* / Q000494:pharmacology; D006007:Glycogen-Synthase-D Phosphatase / Q000378:metabolism*; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008387:Marine Toxins; D052998:Microcystins; D009765:Obesity / Q000201:enzymology* / Q000473:pathology; D010456:Peptides, Cyclic / Q000494:pharmacology; D054645:Protein Phosphatase 1; D051381:Rats; D011924:Rats, Zucker
D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; D006006:Glycogen Synthase; D054645:Protein Phosphatase 1; D006007:Glycogen-Synthase-D Phosphatase; C057862:cyanoginosin LR; D005947:Glucose