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 glucokinas e and GLUT2 glucose transporter gene expression in pancreatic B-cells and liver has been studied in vivo in the rat. Glucokinase mRNA was qu antified 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 starva tion for 2 days and was induced 3-fold by short-term treatment (1 h) o f the rats with oral glucose (4 g/kg body wt.). In contrast the sulpho nylurea compound glibenclamide (0.1 mg/kg body wt.) did not significan tly stimulate glucokinase gene expression in pancreatic B-cells. But g libenclamide caused a 4-fold increase of glucokinase mRNA in liver whi ch was abolished by concomitant administration of diazoxide, a drug wh ich antagonizes glibenciamide-stimulated insulin secretion. GLUT2 gene expression was decreased by 50% 4 in pancreatic B-cells and liver aft er starvation of the rats for 2 days. Neither short-term treatment (1 h) with glucose nor glibenclamide resulted in a significant increase o f GLUT2 gene expression in pancreatic B-cells and liver. The results s uggest that it is glucose which stimulates glucokinase gene expression in pancreatic B-cells whereas the transcriptional regulation of the g lucokinase gene in liver is directed by insulin.