Tissue-specific correction of lipogenic enzyme gene expression in diabetic rats given vanadate

Abstract

SummaryVanadium 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 reverses the impaired expression of genes coding for key enzymes of lipogenesis 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 partially corrected the low thyroid hormone concentrations. In untreated diabetic animals, hepatic mRNA levels of acetyl-CoA carboxylase and fatty acid synthase were reduced by more than 80 and 90 %, respectively, in close correlation with changes in enzyme activities. Three weeks of vanadate treatment totally restored acetyl-CoA carboxylase mRNA and partially restored fatty acid synthase mRNA (71% of control levels). The activities of both lipogenic enzymes were increased 3.5 to 4-fold, to reach 45 to 65 % of control values. By contrast, in white adipose tissue, vanadate modified neither expression nor activity of both lipogenic enzymes, which remained blunted (< 10 % of control levels). In conclusion, vanadate treatment partially restores the activities of two key lipogenic enzymes in liver, but not in white adipose tissue, of diabetic rats. This correction results from a reversal of impaired pre-translational regulatory mechanisms possibly mediated by an improvement of thyroid function and a selective restoration of liver glycolytic flux. [Diabetologia (1994[Diabetologia ( ) 37:1065[Diabetologia ( -1072

Vanadate Activates Membranous Nonreceptor Protein Tyrosine Kinase in Rat Adipocytes

“…Oral vanadium therapy has been shown to have profound antidiabetic effects in diabetic rodents that do not respond at all to insulin (31)(32)(33)(34)(35)(36)(37)(38)(39), and several clinical studies have been initiated with encouraging results (40)(41)(42). Our studies seem to explain how vanadate overcomes insulin resistance as it utilizes alternative (insulin-independent) mechanisms to manifest the metabolic effects of insulin.…”

Molecular and Cellular Determinants of Triglyceride Availabilitya

“…The nutritional status of the organism, closely allied to changes in circulating insulin concentrations, appears to be the major determinant of the rate of lipogenesis. Lipogenesis is high in the fed state and following carbohydrate administration, 14–41 whereas it is suppressed by fasting, 27 high‐fat diets, 29–31 and insulin deficiency 38 …”

“…In streptozotocin‐induced diabetes associated with altered TG levels, gene expression for lipogenic enzymes in both liver and white adipose tissue (WAT) was markedly decreased 38 . On the contrary, the improvement of diabetes with vanadate treatment normalized mRNA levels only in liver, but not in WAT, 38 supporting the role of tissue specificity for the regulation of lipogenesis. Refeeding and insulin treatment of streptozotocin‐treated (STZ) diabetic rats normalized the activity and gene expression of lipogenic enzymes in both the adipose tissue and liver 38 …”

Therapeutic Exploration of Vanadium-Aspirin Coordination Metal Complex Against Diabetic Cataract Exacerbated by Nicotine

“…In current study, we had taken Vanadyl chloride as the central ion and aspirin as the ligand for synthesis of Vanadium-Aspirin coordination metal complex and evaluate its efficacy as a potent anticataractogensis pharmacotheruputical agent. The rationale for selection of Vanadyl chloride is the insulinomimetic nature of vanadium which had been proved by various studies [18][19][20][21]. Aspirin had been one of the unexplored agents in pharmacotheruputic approach in the management of diabetic cataract.…”