Date of Award
Master of Science
Dr. Susan Stapleton
Dr. David Reinhold
Dr. Christine Byrd
Masters Thesis-Open Access
Glucose-6-phosphate dehydrogenase (G6PDH) is a key enzyme of the pentose phosphate pathway. It controls the carbon flow through this pathway, producing reducing equivalents in the form of NADPH to meet the cellular need for reductive biosynthesis and the maintenance of the cellular redox state. Hepatic expression of G6PDH has been shown to be regulated by hormones, nutrients and some growth factors, however the mechanism by which these factors regulate G6PDH gene expression has not been characterized. Here we investigate the mechanism by which insulin and its mimetics, selenate and vanadate, regulate G6PDH gene expression.
Insulin exerts its tissue specific affect by binding to the cell surface receptor initiating a phosphorylation cascade that reaches a variety of cytosolic and nuclear targets. Using well characterized inhibitors of the insulin signal transduction pathway we demonstrate that PI 3-K and S6K are essential for insulin to regulate G6PDH gene expression, where as the proteins of the Ras/Raf/MAPK pathway are not required. Furthermore, we show that the mimetics, selenate and vanadate, utilize different proteins of the insulin signaling cascade to regulate G6PDH gene expression.
Jivarj, Sanjay M., "Mechanism by Which Insulin and Its Mimetics, Selenite and Vanadate, Regulate Glucose-6-Phosphate Dehydrogenase Gene Expression" (1998). Master's Theses. 4502.