Regulation of the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase by insulin

In hypophysectomized--diabetic rats full restoration of hepatic HMG-CoA reductase activity required administration of both triiodothyronine and insulin. Giving triiodothyronine alone resulted in full restoration of reductase mRNA and immunoreactive protein but not of enzyme activity. Increasing the ratio of dithiothreitol to microsomal protein resulted in full HMG-CoA reductase activity. With 5mM glutathione, HMG-CoA reductase activity was 5 to 10 fold higher in non-diabetic animals. The data suggest that insulin acts by increasing the portion of HMG-CoA reductase present in its active free sulfhydryl form.