Decreased insulin-generation of pyruvate dehydrogenase inhibitor in insulin resistant states.
Insulin resistance produced in rats by feeding a high fat diet or by dexamethasone administration (50 micrograms/day, sc for 4 days) resulted in 50-70% decrease in the generation of pyruvate dehydrogenase inhibitor by insulin exposed liver particulate fractions. The inhibition was dose dependent. Treatment of insulin mediator preparations with neuraminidase and B-D-galactosidase resulted in inactivation of the pyruvate dehydrogenase inhibitor. Presence of exogenous enzyme substrates during enzyme digestion partially protected the inhibitor from inactivation. Protease treatment did not affect the inhibitor while the stimulatory activity of the insulin mediator was abolished by trypsin treatment. These results together with the previous report suggest that insulin resistance results in a decrease in the generation of both of the mediators of insulin action. This may result from a decrease in insulin binding, shown earlier, or from a decrease in precursor availability.
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004040:Dietary Carbohydrates / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology; D005696:Galactosidases / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008297:Male; D009439:Neuraminidase / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D007328:Insulin; D011768:Pyruvate Dehydrogenase Complex; D003907:Dexamethasone; D005696:Galactosidases; D009439:Neuraminidase