Date of Award

12-1995

Degree Name

Master of Arts

Department

Chemistry

First Advisor

Dr. Susan R. Stapleton

Second Advisor

Dr. Michael E. McCarville

Third Advisor

Dr. Donald R. Schreiber

Access Setting

Masters Thesis-Open Access

Abstract

Many researchers have shown that selenate (SeO42-) and vanadate (VO42-) have insulin-mimetic effects in certain biological processes. These mimetic effects include increasing glucose transport, regulating glycolytic enzymes, normalizing plasma glucose levels and activities of insulin regulated enzymes in diabetic rats. To clarify the functions and roles of these insulin-mimetics in different insulin-regulated metabolic pathways, the expression of the genes for glucose-6-phosphate dehydrogenase (G6PDH) and fatty acid synthase (FAS) were investigated. G6PDH is a key enzyme in the pentose phosphate pathway and is also involved in lipogenic metabolism by providing 55-70% of the NADPH utilization in fatty acid biosynthesis. FAS is a multifunctional lipogenic enzyme which utilizes NADPH in the reaction to catalyze the conversion from acetyl-CoA to palmitate. Our goal was to examine the effects of sodium vanadate and sodium selenate on lipogenic metabolism in two insulin responsive systems: isolated rat hepatocytes in culture and streptozotocin-induced diabetic rats. The focus of my study was to elucidate if these agents acted in an insulin-like manner with respect to inducing the mRNA level for both G6PDH and FAS.

Results showed that selenate and vanadate have similar effects to that of insulin on G6PDH and FAS mRNA expression. The effects of the mimetics in combination with insulin were the same suggesting the mimetics may be acting via the same mechanism.

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