Effect of Dexamethasone on Adipose Tissue and Liver Pyruvate Dehydrogenase and Its Stimulation by Insulin-Generated Chemical Mediator*

Abstract

Rats were treated with dexamethasone (50 .mu.g/day, s.c.) for 4 days [glucocorticoid administration results in insulin resistance]. Total pyruvate dehydrogenase (PDH) and insulin-stimulated PDH 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 mitochondrial 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. Apparently 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.