Colchicine inhibition of insulin induction of stearoyl-CoA desaturase and fatty acid synthetase in cultured avian liver explants.
Chicken embryo liver explants cultured in chemically defined medium in the absence of serum provide a unique system to probe into the mechanism of insulin induction of lipogenic enzymes. Colchicine at concentrations of 0.2 and 1 microM in the culture medium caused inhibition of insulin induction of stearoyl-CoA desaturase and fatty acid synthetase by 50 and 90%, respectively. As measured by immunochemical techniques, the inhibition of the induction of these two enzyme systems resulted from the decreased content of the delta 9-terminal desaturase component of the stearoyl-CoA desaturase and the fatty acid synthetase. Colchicine, however, had no effect on the general protein synthesis, nor did it affect the malic enzyme, which is induced by triiodothyronine but not by insulin. Also, colchicine had no influence on the binding of 125I-insulin to isolated plasma membrane. Pretreatment of liver explants with insulin for 0.5-1 h and subsequent incubation in insulin-free media for 48 h resulted in induction of the desaturase and fatty acid synthetase. However, inclusion of colchicine in the media for 3 h subsequent to the treatment with insulin completely abolished the inductive effect of insulin, suggesting that colchicine affects events occurring subsequent to insulin binding to the cell surface membranes. Since lumicolchicine, an inactive isomer of colchicine, had no effect on insulin action, it is suggested that the inhibition of insulin induction of the desaturase and synthetase is related to the depolymerizing action of colchicine. Therefore, in eliciting long-term responses to insulin, microtubular integrity of the cell may be required for the transfer of a putative from cell surface insulin receptor to intracellular sites.
D000818:Animals; D002642:Chick Embryo; D003078:Colchicine / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D044943:Fatty Acid Desaturases / Q000096:biosynthesis*; D064429:Fatty Acid Synthases / Q000096:biosynthesis*; D007120:Immunochemistry; D007328:Insulin / Q000494:pharmacology*; D007329:Insulin Antagonists; D008099:Liver / Q000201:enzymology*; D008291:Malate Dehydrogenase / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects; D009924:Organ Culture Techniques; D013230:Stearoyl-CoA Desaturase / Q000096:biosynthesis*; D014284:Triiodothyronine / Q000494:pharmacology
D007328:Insulin; D007329:Insulin Antagonists; D014284:Triiodothyronine; D008291:Malate Dehydrogenase; D044943:Fatty Acid Desaturases; D013230:Stearoyl-CoA Desaturase; D064429:Fatty Acid Synthases; D003078:Colchicine