EFFECTS OF DIABETES ON THE EXPRESSED AND TOTAL ACTIVITIES OF 3-HYDROXY-3-METHYLGLUTARYL-COA REDUCTASE IN RAT-LIVER INVIVO - REVERSAL BY INSULIN-TREATMENT

1. The expressed and total activities of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase (EC 1.1.1.34) were measured in microsomal fractions prepared from cold-clamped liver samples [Easom and Zammit (1984) Biochem. J. 220, 733-738] from control or insulin-treated diabetic animals. 2. Streptozotocin-induced diabetes resulted in a marked decrease in total activity of HMG-CoA reductase and in the fraction of the enzyme in the active form, but appreciable effects were only observed in the liver of animals in which the blood glucose was above 20mM. Intravenous infusion of insulin into diabetic rats resulted in a rapid (< 20 min) and total dephosphorylation of the enzyme in vivo without any change in total activity. 4. Longer-term (4h) treatment with insulin (injected intraperitoneally) produced a rapid increase in expressed/total HMG-CoA reductase activity ratio to about 90%, followed after a lag of 2-3 h, by a 5-6-fold increase in total activity. 5. These observations are discussed with respect to the possible role of insulin in generating and maintaining the respective diurnal rhythms in total and in expressed/total HMG-CoA reductase activity ratio observed for normal animals in vivo [Easom and Zammit (1984) Biochem. J. 220, 739-745].