IN-VIVO EFFECTS OF VANADATE ON HEPATIC GLYCOGEN METABOLIZING AND LIPOGENIC ENZYMES IN INSULIN-DEPENDENT AND INSULIN-RESISTANT DIABETIC ANIMALS

The insulin-mimetic action of vanadate is well established but the exa ct mechanism by which it exerts this effect is still not clearly under stood. The role of insulin in the regulation of hepatic glycogen metab olizing and lipogenic enzymes is well known. In our study, we have, th erefore, examined the effects of vanadate on these hepatic enzymes usi ng four different models of diabetic and insulin-resistant animals. Va nadate normalized the blood glucose levels in all animal models. In st reptozotocin-induced diabetic rats, the amount of liver glycogen and t he activities of the active-form of glycogen synthase, both active and inactive-forms of phosphorylase, and lipogenic enzymes like glucose 6 -phosphate dehydrogenase and malic enzyme were decreased and vanadate treatment normalized all of these to near normal levels. The other thr ee animal models (db/db mouse, sucrose-fed rats and fa/fa obese Zucker rats) were characterized by hyperinsulinemia, hypertriglyceridemia, i ncreases in activities of lipogenic enzymes, and marginal changes in g lycogen metabolizing enzymes. Vanadate treatment brought all of these values towards normal levels. It should be noted that vanadate shows d ifferential effects in the modulation of lipogenic enzymes activities in type I and type II diabetic animals. It increases the activities of lipogenic enzymes in streptozotocin-induced diabetic animals and prev ents the elevation of activities of these enzymes in hyperinsulinemic animals. The insulin-stimulated phosphorylation of insulin receptor be ta subunit and its tyrosine kinase activity was increased in streptozo tocin-induced diabetic rats after treatment with vanadate. Our results support the view that insulin receptor is one of the sites involved i n the insulin-mimetic actions of vanadate.