Dactinomycin inhibitionof dexamethasone action on glucose metabolism in white fat cells

Abstract

1. 1. Dexamethasone inhibited the conversion of [I- 14C]glucose to CO 2 by white fat cells by as much as 79% following a characteristic lag period of about 2 h. 2. 2. Both insulin and cysteine stimulated glucose conversion to CO 2 4-fold; dexamethasone did not diminish the increment in glucose metabolism evoked by either of these agents. 3. 3. Cycloheximide mimicked the inhibitory effect of dexamethasone on basal glucose agents were present at the start of the incubation and labeled CO 2 production of the antibiotic. 4. 4. Dactinomycin almost completely abolished the effect of dexamethasone when both agents were present at the start of the incubation and labeled CO 2 production was measured over the final 2 h of a 4-h incubation period. When dactinomycin was added at 1 h it inhibited the effect of dexamethasone by 32%. Addition of the antibiotic at 2 h was without effect on the action of dexamethasone in these experiments. 5. 5. Dexamethasone caused a 20% decrease in trichloroacetic acid-insoluble radioactivity of cells which were labeled with [ 3H]uridine during the isolation period and subsequently incubated without label for 3 h. This effect was not observed at 1.5 h. 6. 6. These data are compatible with the concept that glucocorticoids inhibit glucose metabolism in white fat cells by a process requiring cellular RNA synthesis and which involves either (a) the inhibition of the synthesis of a protein (s) necessary for an insulin-independent step in glucose utilization or (b) the synthesis of a protein(s) inhibitory to glucose metabolism.