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Carbon flux via the pentose phosphate pathway regulates the hepatic expression of the glucose-6-phosphatase and phosphoenolpyruvate carboxykinase genes in conscious rats.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 1998 Jan 02; Vol. 273 (1), pp. 228-34. - Publication Year :
- 1998
-
Abstract
- Hepatic gene expression of P-enolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (Glc-6-Pase) is regulated in response to changes in the availability of substrates, in particular glucose (Glc; Massillon, D., Barzilai, N., Chen, W., Hu, M., and Rossetti, L. (1996) J. Biol. Chem. 271, 9871-9874). We investigated the mechanism(s) in conscious rats. Hyperglycemia per se caused a rapid and marked increase in Glc-6-Pase mRNA abundance and protein levels. By contrast, hyperglycemia decreased the abundance of PEPCK mRNA. Importantly, inhibition of glucokinase activity by glucosamine infusion blunted both the stimulation of Glc-6-Pase and the inhibition of PEPCK gene expression by Glc, suggesting that an intrahepatic signal (metabolite) generated by the metabolism of glucose at or beyond Glc-6-P was responsible for the regulatory effect of Glc. The effect of Glc on the L-type pyruvate kinase gene is mediated by xylulose-5-P (Doiron, B., Cuif, M., Chen, R., and Kahn, A. (1996) J. Biol. Chem. 271, 5321-5324). Thus, we next investigated whether an isolated increase in the hepatic concentration of this metabolite can also reproduce the effects of Glc on Glc-6-Pase and PEPCK gene expression in vivo. Xylitol, which is directly converted to xylulose-5-P in the liver, was infused to raise the hepatic concentration of xylulose-5-P by approximately 3-fold. Xylitol infusion did not alter the levels of Glc-6-P and of fructose-2,6-biphosphate. However, it replicated the effects of hyperglycemia on Glc-6-Pase and PEPCK gene expression and resulted in a 75% increase in the in vivo flux through Glc-6-Pase (total glucose output).
- Subjects :
- Animals
Gene Expression Regulation, Enzymologic drug effects
Glucose metabolism
Male
Phosphorylation
RNA, Messenger genetics
Rats
Rats, Sprague-Dawley
Xylitol administration & dosage
Xylitol pharmacology
Carbon metabolism
Glucose-6-Phosphatase genetics
Liver enzymology
Pentose Phosphate Pathway
Phosphoenolpyruvate Carboxykinase (ATP) genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 273
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 9417069
- Full Text :
- https://doi.org/10.1074/jbc.273.1.228