INSULIN-LIKE EFFECTS OF VANADATE AND SELENATE ON THE EXPRESSION OF GLUCOSE-6-PHOSPHATE-DEHYDROGENASE AND FATTY-ACID SYNTHASE IN DIABETIC RATS

Insulin is capable of regulating cellular and metabolic processes as w ell as gene expression. In recent years, enthusiasm has surfaced for u sing insulin-mimetics to study the mechanism of action of insulin. Van adate and selenate are two compounds that have been found to mimic the action of insulin on control of blood glucose levels in vivo. Vanadat e has also been shown to regulate the expression of several enzymes bo th in vivo and in vitro, however, studies concerning selenate's abilit y to regulate expression have not been reported. In this study we show that administration of vanadate or selenate to streptozotocin-induced diabetic rats not only normalizes blood glucose levels similarly to i nsulin but also positively affects the expression of two key metabolic enzymes, glucose-6-phosphate dehydrogenase (G6PDH) and fatty acid syn thase (FAS). Both G6PDH and FAS activity are significantly decreased i n diabetic animals compared to non-diabetic control. Treatment of the diabetic animals with either insulin, vanadate or selenate restored bo th activities to about 80-90% of control. All treatment conditions exh ibited activities significantly higher than those determined for the d iabetic group but did not differ significantly from each other. Increa ses in G6PDH or FAS activity are due to increases in mRNA level. Incre ase in both G6PDH and FAS mRNA was comparable to the observed increase in activity suggesting that regulation of expression by the mimetics occurs pretranslationally.