Date of Award
Master of Science
Dr. Susan Stapleton
Dr. Cindy Hoorn
Dr. David Reinhold
Masters Thesis-Open Access
Circulating high glucose levels are believed to cause oxidative stress which is implicated in a number of pathological conditions such as cancer, aging, and diabetes. Oxidative stress regulates the expression of glucose-6-phosphate dehydrogenase (G6PDH), the key enzyme in the pentose phosphate pathway which provides reducing equivalents in the form of NADPH. These reducing equivalents are also required by fatty acid synthase (FAS), the enzyme which catalyzes fatty acid biosynthesis. We examined whether glucose, a known inducer of oxidative stress, could regulate either G6PDH or FAS activity in primary rat hepatocytes. We tested the effects of glucose alone or in combination with insulin or selenate. Insulin and selenate are known to induce G6PDH and FAS expression.
Growth factor and stress mediated regulation of gene expression can utilize the MAP kinase signal pathway, therefore we examined if glucose effects the phosphorylation of the insulin receptor and Shc, two proteins of this pathway.
Our results indicate that G6PDH activity is regulated by glucose concentration, but this does not affect the insulin- or selenate-induced increase in G6PDH activity. The effect of glucose concentration alone or in combination with insulin- and selenate-induced FAS activity was inconclusive. Insulin and selenate caused phosphorylation of. the insulin receptor and Shc, but varying the glucose concentration had no effect.
Arkwright, Daryl, "Glucose Mediated Effects on Glucose-6-Phosphate Dehydrogenase Expression" (1998). Masters Theses. 5319.