Date of Defense

12-5-2003

Department

Chemistry

First Advisor

Susan Stapleton, Chemistry

Second Advisor

Dave Reinhold, Chemistry

Third Advisor

Michael Barcelona, Chemistry

Abstract

Insulin is a very important metabolic regulator in the body. Insulin induces its effects by binding to a receptor on the plasma membrane, resulting in autophosphorylation of the receptor and phosphorylation of key proteins involved in the signal cascade. One of the key functions of insulin lies in the stimulation of glucose uptake into the cells for use in metabolic pathways such as glycolysis and the pentose phosphate pathway. This occurs mainly through the activation of the phosphatidylinositol (PI) 3-kinase pathway. Akt, a significant signal protein downstream of PI-3 kinase, is a serine/threonine kinase that recently has been implicated in mediating a variety of cellular functions including cell survival, cell proliferation, and glucose metabolism. Since Akt lies downstream of PI-3 kinase, it may be involved in mediating insulin-induced glucose metabolism by regulating the expression of vital enzymes necessary for metabolic pathways. To determine the involvement of Akt in glucose metabolism, we investigated the role of Akt in the expression of glucose-6-phosphate dehydrogenase (G6PDH), a key protein in an insulinregulated metabolic pathway. Additionally, our interest lies in the further demonstration of selenium as an effective insulin-mimetic compound by investigating the effects of selenium on Akt activity and G6PDH expression. We were able to demonstrate that both insulin and selenium increased Akt activity and G6PDH expression in H4IIE cells. By using specific Akt inhibitors, both insulin and selenium-induced Akt activity were diminished. Subsequently, we also observed that in transiently transfected liver cells, inhibition of insulin-induced Akt activity resulted in a decrease in the expression of G6PDH.

Access Setting

Honors Thesis-Campus Only

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