ACUTE REGULATION OF HEPATIC GLUTATHIONE-S-TRANSFERASE BY INSULIN AND GLUCAGON

The intravenous administration of insulin plus glucose in anesthetized rats caused, within 30 min, an increase of about 56% in hepatic cytos olic glutathione S-transferase (GST) activity, but it did not affect t he microsomal enzyme. The injection of glucagon resulted, at the same time, in a 43% drop in the hepatic cytosolic GST, without affecting th e microsomal GST. The insulin-dependent increase in cytosolic GST acti vity was abolished by the pretreatment of the animals with an inhibito r of protein synthesis (cycloheximide). A kinetic analysis revealed a non-competitive inhibition caused by glucagon upon the cytosolic enzym e. In addition, the presence of insulin did not interfere with the eff ectiveness of glucagon, and vice versa. We propose that: (1) the effec t of insulin on hepatic cytosolic GST activity requires protein synthe sis; (2) glucagon produces an inhibition of hepatic cytosolic GST, whi ch could be mediated by cytosolic effecters such as adenosine 3'-5'-cy clic monophosphate (cAMP); (3) the effects of glucagon and insulin wer e not mutually exclusive; (4) hepatic microsomal GST is regulated by d ifferent mechanism(s).