Effects of glucose refeeding and glibenclamide treatment on glucokinase and GLUT2 gene expression in pancreatic B-cells and liver from rats.

The mutual role of glucose and insulin in the regulation of glucokinase and GLUT2 glucose transporter gene expression in pancreatic B-cells and liver has been studied in vivo in the rat. Glucokinase mRNA was quantified by competitive reverse-transcriptase PCR analysis, and GLUT2 mRNA by Northern-blot analysis in total RNA fractions. As in the liver, glucokinase mRNA decreased by 64% in pancreatic B-cells after starvation for 2 days and was induced 3-fold by short-term treatment (1 h) of the rats with oral glucose (4 g/kg body wt.). In contrast the sulphonylurea compound glibenclamide (0.1 mg/kg body wt.) did not significantly stimulate glucokinase gene expression in pancreatic B-cells. But glibenclamide caused a 4-fold increase of glucokinase mRNA in liver which was abolished by concomitant administration of diazoxide, a drug which antagonizes glibenclamide stimulated insulin secretion. GLUT2 gene expression was decreased by 50% in pancreatic B-cells and liver after starvation of the rats for 2 days. Neither short-term treatment (1 h) with glucose nor glibenclamide resulted in a significant increase of GLUT2 gene expression in pancreatic B-cells and liver. The results suggest that it is glucose which stimulates glucokinase gene expression in pancreatic B-cells whereas the transcriptional regulation of the glucokinase gene in liver is directed by insulin.