Interactions of insulin and dexamethasone in the control of pyruvate kinase activity and glucose metabolism in sheep adipose tissue.
1. The Vmax. activity of pyruvate kinase of sheep adipose tissue increased during tissue culture up to 48 h; the increase was blocked by actinomycin D (an inhibitor of transcription) and was promoted by insulin and antagonized by dexamethasone. 2. In contrast with their effects on pyruvate kinase, insulin and dexamethasone acted synergistically to increase the activity of glucose-6-phosphate dehydrogenase of sheep adipose tissue maintained in culture. 3. Insulin stimulated, whereas dexamethasone inhibited, glucose utilization by sheep adipose tissue maintained in culture; the two agents were mutually antagonistic, and their effects were prevented by actinomycin D. 4. Antimycin A (an inhibitor of the electron-transport chain) stimulated glucose uptake and lactate output by sheep adipose tissue in the presence of dexamethasone and insulin, suggesting that the effects of dexamethasone on glucose utilization by sheep adipose tissue were not due to an inhibition of glucose transport. 5. Comparison of these findings with previous studies on the endocrine control of hepatic pyruvate kinase shows that there are major differences in the control of these Vmax. activities in liver and adipose tissue. 6. Although glucocorticoid hormones inhibit glucose utilization themselves and can antagonize the stimulatory effects of insulin on glucose utilization in adipose tissue from both sheep and rats, there appear to be major differences in the sites of action of these hormones in the two species.
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Department of Biochemistry, University of Nottingham Medical School, Queen's Medical Centre, U.K.
Taylor
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Brindley
D N
DN
Vernon
R G
RG
D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D046508:Culture Techniques; D003907:Dexamethasone / Q000494:pharmacology*; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism; D006854:Hydrocortisone / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D011770:Pyruvate Kinase / Q000378:metabolism*; D012756:Sheep; D013806:Theophylline / Q000494:pharmacology
D007328:Insulin; D007773:Lactates; D019344:Lactic Acid; D003907:Dexamethasone; D013806:Theophylline; D011770:Pyruvate Kinase; D005947:Glucose; D005990:Glycerol; D006854:Hydrocortisone