TISSUE-SPECIFIC CORRECTION OF LIPOGENIC ENZYME GENE-EXPRESSION IN DIABETIC RATS GIVEN VANADATE

Vanadium is a potent insulinomimetic agent. In vivo, its blood glucose lowering action in insulin-deficient diabetic rats is associated with corrected expression of genes involved in hepatic glucose metabolism. In this study, we investigated whether vanadate treatment also revers es the impaired expression of genes coding for key enzymes of lipogene sis in diabetic liver and white adipose tissue. Oral administration of vanadate to streptozotocin-rats caused a 55 % fall in plasma glucose levels after feeding without modifying low insulinaemia. It also parti ally corrected the low thyroid hormone concentrations. In untreated di abetic animals, hepatic mRNA levels of acetyl-CoA carboxylase and fatt y acid synthase were reduced by more than 80 and 90 %, respectively, i n close correlation with changes in enzyme activities. Three weeks of vanadate treatment totally restored acetyl-CoA carboxylase mRNA and pa rtially restored fatty acid synthase mRNA (71 % of control levels). Th e activities of both lipogenic enzymes were increased 3.5 to 4-fold, t o reach 45 to 65 % of control values. By contrast, in white adipose ti ssue, vanadate modified neither expression nor activity of both lipoge nic enzymes, which remained blunted (< 10 % of control levels). In con clusion, vanadate treatment partially restores the activities of two k ey lipogenic enzymes in liver, but not in white adipose tissue, of dia betic rats. This correction results from a reversal of impaired pre-tr anslational regulatory mechanisms possibly mediated by an improvement of thyroid function and a selective restoration of liver glycolytic fl ux.