Effect of dexamethasone on adipose tissue and liver pyruvate dehydrogenase and its stimulation by insulin-generated chemical mediator.
Rats were treated with dexamethasone (50 micrograms/day, sc) for 4 days. Total pyruvate dehydrogenase (PDH) and insulin-stimulated PDHa activities were decreased in fat pads from dexamethasone-treated rats compared to control values. Coincubation experiments with adipocyte mitochondria, plasma membrane, and insulin demonstrated decreased stimulation of PDH in preparations from dexamethasone-treated rats. The responsiveness of the mitochondrial PDH system to insulin and control rat plasma membranes was not different in glucocorticoid-treated adipocyte preparations compared to controls. Liver mitochondria from dexamethasone-treated rats demonstrated decreased basal enzyme activity and a decreased percentage of stimulation of PDH when supernatants from insulin-exposed liver particulate fractions were tested. These experiments suggest that insulin resistance produced by glucocorticoid treatment, like that resulting from fat feeding, is accompanied by a decrease in the capacity of adipocyte and liver plasma membranes to generate PDH activator in response to insulin.
D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004789:Enzyme Activation; D006019:Glycolysis / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism* / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin; D011506:Proteins; D011768:Pyruvate Dehydrogenase Complex; C029131:pyruvate dehydrogenase activator; D003907:Dexamethasone