IMPROVEMENT OF GLUCOSE AND LIPID-METABOLISM IN DIABETIC RATS TREATED WITH MOLYBDATE

Molybdenum mimics certain insulin actions in vitro. We have investigat ed the effects of oral administration of Na2MoO4 (Mo) for 8 wk on carb ohydrate and lipid metabolism in streptozotocin-diabetic rats. Mo decr eased hyperglycemia and glucosuria by 75% and corrected the elevation of plasma nonesterified fatty acids. Tolerance to glucose loads was im proved, and glycogen stores were replenished. These effects were not d ue to a rise of insulinemia. In liver, Mo restored the blunted mRNA an d activity of glucokinase and pyruvate kinase and decreased to normal phosphoenolpyruvate carboxykinase values. Finally, Mo totally reversed the low expression and activity of acetyl-CoA carboxylase and fatty a cid synthase in Liver, but not in white adipose tissue. In conclusion, Mo exerts a marked blood glucose-lowering effect in diabetic rats by an insulin-like action. This effect results in part from a restoration of hepatic glucose metabolism and is associated with a tissue-specifi c correction of lipogenic enzyme gene expression, both processes being essentially mediated by reversal of impaired pretranslational regulat ory mechanisms. These observations raise new therapeutic perspectives in diabetes, particularly in the insulin-resistant condition.