Induction of Hepatic Glucose-6-Phosphate Dehydrogenase by Glucose

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Holmes, Alison J.
Glucose Transporters; Glucose Action; enzyme effect; luciferase reporter gener
thesis / dissertation description
The effect of glucose alone on the enzyme glucose-6-phosphate dehydrogenase (G6PDH) was determined in hepatocytes maintained in a chemically-defined medium. Glucose was found to increase endogenous G6PDH activity in a concentration-dependent manner up to 3.5-fold at 30 mM in stable BRL cells incubated for 41.5h in glucose. Glucose also increased the expression of a luciferase reporter gene construct driven by the G6PDH promoter that was tran siently transfected into primary rat hepatocytes. This increase in expression of the reporter plasmid reached a maximum of 2.5-fold at 30 mM glucose. Activities of both the endogenous enzyme and the promoter increased remarkably in stably-transfected BRL cells incubated for 6h in glucose. These data show glucose to induce G6PDH, at least in part, at the level of gene expression, and they offer new insight into the roles of glucokinase and glucose transporters in the mechanism of glucose action.