GLUCOSE REGULATES IN-VIVO GLUCOSE-6-PHOSPHATASE GENE-EXPRESSION IN THE LIVER OF DIABETIC RATS

Overproduction of glucose by the liver is the major cause of fasting h yperglycemia in both insulin-dependent and non-insulin-dependent diabe tes mellitus. The distal enzymatic step in the process of glucose outp ut is catalyzed by the glucose-6-phosphatase complex. We show here tha t 90% partially pancreatectomized diabetic rats have a >5-fold increas e in the messenger RNA and a 3-4-fold increase in the protein level of the catalytic subunit of glucose-6-phosphatase in the liver. Normaliz ation of the plasma glucose concentration in diabetic rats with either insulin or the glycosuric agent phlorizin normalized the hepatic gluc ose-6-phosphatase messenger RNA and protein within similar to 8 h. Con versely, phlorizin failed to decrease hepatic glucose-6-phosphatase ge ne expression in diabetic rats when the fall in the plasma glucose con centration was prevented by glucose infusion, These data indicate that in vivo gene expression of glucose-6-phosphatase in the diabetic live r is regulated by glucose independently from insulin, and thus prolong ed hyperglycemia may result in overproduction of glucose via increased expression of this protein.