Hexose-independent activation of glycogen synthase and pyruvate dehydrogenase by insulin is dissociated in the mouse BC3H-1 cell line.
We have studied the effects of insulin on several aspects of cell metabolism in the insulin-sensitive, nonfusing muscle cell line BC3H-1. In the absence of exogenous hexose, insulin did not alter basal glycogen synthase percentage I activity, or attenuate the increase in intracellular cAMP content, the activation of glycogen phosphorylase a, or the decrease in glycogen synthase I brought about by beta-adrenergic receptor activation with epinephrine. In contrast, both insulin and the tumor-promoting phorbol ester, tetradecanoylyl phorbol acetate markedly increased mitochondrial pyruvate dehydrogenase activity in the absence of hexose. Both glycogen synthase phosphatase and glycogen synthase kinase activities were present in BC3H-1 cell extracts and were regulated in the expected manner by glucose 6-phosphate and cAMP, respectively. Since the pattern of partial insulin resistance seen in BC3H-1 myocytes would require that several potentially insulin-sensitive enzymes be insensitive to insulin-generated signals, the most likely explanation for these data is that the myocytes are defective in some mechanism of insulin signaling which is independent of the mechanism for pyruvate dehydrogenase activation.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D006006:Glycogen Synthase / Q000378:metabolism*; D006601:Hexoses / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008809:Mice, Inbred C3H; D009206:Myocardium / Q000201:enzymology; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000502:physiology
D006601:Hexoses; D007328:Insulin; D011768:Pyruvate Dehydrogenase Complex; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D006006:Glycogen Synthase; D015056:1-Methyl-3-isobutylxanthine