Inhibition of acetyl-CoA carboxylase activity in isolated rat adipocytes incubated with glucagon. Interactions with the effects of insulin, adrenaline and adenosine deaminase.
1. Adipocytes isolated from epididymal fat-pads of fed rats were incubated with different concentrations of glucagon, insulin, adrenaline and adenosine deaminase, and the effects of these agents on the ;initial' activity of acetyl-CoA carboxylase in the cells were studied. 2. Glucagon (at concentrations between 0.1 and 10nm) inhibited acetyl-CoA carboxylase activity. Maximal inhibition was approx. 70% of the ;control' activity in the absence of added hormone, and the concentration of hormone required for half-maximal inhibition was 0.3-0.5nm-glucagon. 3. Incubation of cells with adenosine deaminase resulted in a similar inhibition of acetyl-CoA carboxylase activity. Preincubation of adipocytes with adenosine deaminase did not alter either the sensitivity of carboxylase activity to increasing concentrations of glucagon or the maximal extent of inhibition. 4. Adrenaline inhibited acetyl-CoA carboxylase to the same extent as glucagon. Preincubation of the cells with glucagon did not alter the sensitivity of enzyme activity to adrenaline or the degree of maximal inhibition. 5. Insulin activated the enzyme by 70-80% of ;control' activity. Preincubation of the cells with glucagon did not alter the concentration of insulin required to produce half the maximal stimulatory effect (about 12muunits of insulin/ml). The effects of insulin and glucagon appeared to be mediated completely independently, and were approximately quantitatively similar but opposite. These characteristics resulted in the mutual cancellation of the effects of the two hormones when they were both present at equally effective concentrations. 6. The implications of these findings with regard to current concepts about the mechanism of regulation of acetyl-CoA carboxylase and to the regulation of the enzyme in vivo are discussed.
D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000243:Adenosine Deaminase / Q000494:pharmacology*; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008025:Ligases / Q000037:antagonists & inhibitors*; D008297:Male; D009700:Nucleoside Deaminases / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D005934:Glucagon; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase; D008025:Ligases; D000103:Acetyl-CoA Carboxylase; D004837:Epinephrine