Date of Award

12-1997

Degree Name

Master of Science

Department

Biological Sciences

First Advisor

Dr. Susan R. Stapleton

Second Advisor

Dr. David Reinhold

Third Advisor

Dr. Cindy Hoorn

Access Setting

Masters Thesis-Open Access

Abstract

Insulin mimetics are compounds that mimic the action of insulin in the body and are currently being studied as possible therapeutic agents against diabetes. Vanadium has been identified as an element with insulin-like properties with regard to metabolic processes such as lowering blood glucose levels. Few studies have implicated vanadium in mitogenic actions such as cell growth and differentiation. We studied the action of vanadate on the expression of the insulin-induced SRE, a cis-element of the well-characterized mitogenic gene c-fos. We measured this expression by means of a plasmid containing the reporter gene luciferase linked to the sequences from c-fos containing the SRE (SRE-Luc). We also examined activation of signal proteins that might be responsible for the insulin induction of SRE-Luc.

This study showed that insulin increased expression of SRE-Luc in a time-dependent fashion, vanadate had no effect on the expression of SRE-Luc. Use of inhibitors of the PI3K and MAPK pathways suggested that PI3K is necessary for insulin induction of SRE-Luc and PI3K maybe located somewhere between Ras and MEK. The use of inhibitors also helped determine that both, MAPK and PI3K pathway proteins may also be necessary for the insulin-induced expression of SRE-Luc. Additionally, we assessed JNK activity in the presence of insulin and vanadate. Our results indicate that insulin and not vanadate activate JNK, a close relative of MAPK.

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