Triiodothyronine and insulin effects on malic enzyme in hypothyroid and diabetic rats

We examined the effects of T3 and insulin on the activity of hepatic mitochondrial alpha-glycerophosphate dehydrogenase and cytosolic malic enzyme in control, thyroidectomized, thyroidectomized food-restricted, and thyroidectomized diabetic rats. In the three untreated thyroidectomized groups, the decrease in hepatic nuclear T3 content was accompanied by a marked reduction in the levels of alpha-glycerophosphate dehydrogenase and malic enzyme activity. Although the levels of both enzymes were increased by a receptor-saturating dose of T3, the alpha-glycerophosphate dehydrogenase response in the thyroidectomized groups was almost identical to that in controls, whereas that of malic enzyme was reduced to 45-62% of control values. Insulin failed to stimulate the alpha-glycerophosphate dehydrogenase levels in untreated and T3-treated thyroidectomized groups, but caused an increase in malic enzyme activity by 79-130% in untreated thyroidectomized groups, and enhanced the activity of this enzyme to about twice that seen with T3 alone. These effects were independent of changes in nuclear T3 binding parameters. The data suggest that insulin may act on malic enzyme synthesis through its general stimulatory effect on protein synthesis, or by antagonizing factors that inhibit the induction of this enzyme.