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 hyperglycemia in both insulin-dependent and non-insulin-dependent diabetes mellitus. The distal enzymatic step in the process of glucose output is catalyzed by the glucose-6-phosphatase complex. We show here that 90% partially pancreatectomized diabetic rats have a >5-fold increase 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. Normalization of the plasma glucose concentration in diabetic rats with either insulin or the glycosuric agent phlorizin normalized the hepatic glucose-6-phosphatase messenger RNA and protein within approximately 8 h. Conversely, phlorizin failed to decrease hepatic glucose-6-phosphatase gene expression in diabetic rats when the fall in the plasma glucose concentration was prevented by glucose infusion. These data indicate that in vivo gene expression of glucose-6-phosphatase in the diabetic liver is regulated by glucose independently from insulin, and thus prolonged hyperglycemia may result in overproduction of glucose via increased expression of this protein.
Massillon
D
D
Diabetes Research and Training Center and Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Barzilai
N
N
Chen
W
W
Hu
M
M
Rossetti
L
L
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004734:Energy Metabolism; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism*; D005952:Glucose-6-Phosphatase / Q000378:metabolism*; D006943:Hyperglycemia / Q000201:enzymology; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D008297:Male; D010695:Phlorhizin / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D007328:Insulin; D012333:RNA, Messenger; D010695:Phlorhizin; D005952:Glucose-6-Phosphatase; D005947:Glucose