Altered transcriptional regulation of phosphoenolpyruvate carboxykinase in rats following endotoxin treatment.
Open Access
- 1 September 1991
- journal article
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 88 (3) , 811-816
- https://doi.org/10.1172/jci115381
Abstract
The molecular mechanism involved in altered regulation of the rate-limiting enzyme in hepatic gluconeogenesis, phosphoenolpyruvate carboxykinase (PEPCK), during endotoxemia is not completely understood. We examined, therefore, the effect of a nonlethal dose of Escherichia coli endotoxin on PEPCK gene expression in fasted rats. 5 h after endotoxin treatment, the PEPCK transcription rate and the amount of mRNA(PEPCK) were significantly decreased at a time when the insulin/glucagon (I/G) molar ratio and plasma corticosterone levels were significantly increased. Similar results were observed in a time course study, in which altered cAMP induction of PEPCK gene expression paralleled changes in the I/G molar ratio. In diabetic rats treated with endotoxin, PEPCK gene expression was decreased in the absence, however, of an increased I/G molar ratio. This finding indicates that other factors, such as inflammatory mediators or cytokines, alter PEPCK gene transcription during endotoxemia. IL-6, a putative mediator of endotoxin action in the liver, had no effect on PEPCK gene expression in fasted rats, but did decrease cAMP induction of PEPCK gene expression. These results indicate that, during endotoxemia, regulation of PEPCK gene expression is influenced by inflammatory mediators in addition to the classical endocrine hormones. IL-6, however, does not appear to be involved directly in the altered regulation of the PEPCK gene during endotoxemia.Keywords
This publication has 35 references indexed in Scilit:
- 3' noncoding region of phosphoenolpyruvate carboxykinase mRNA contains a glucocorticoid-responsive mRNA-stabilizing element.Proceedings of the National Academy of Sciences, 1989
- Endotoxemia elicits increased circulating beta 2-IFN/IL-6 in man.The Journal of Immunology, 1989
- IL-6/IFN-BETA-2 AS A CIRCULATING HORMONE - INDUCTION BY CYTOKINE ADMINISTRATION IN HUMANS1989
- IL-6 modulates the synthesis of a specific set of acute phase plasma proteins in vivo.The Journal of Immunology, 1989
- FAILURE OF GLUCAGON TO INDUCE HEPATIC PHOSPHOENOLPYRUVATE CARBOXYKINASE IN ENDOTOXIC-SHOCK1988
- Cyclic AMP stabilizes the mRNA for phosphoenolpyruvate carboxykinase (GTP) against degradation.Journal of Biological Chemistry, 1988
- The molecular biology of insulin action on protein synthesis.1987
- Receptors for B cell stimulatory factor 2. Quantitation, specificity, distribution, and regulation of their expression.The Journal of Experimental Medicine, 1987
- Purification and NH2-terminal amino acid sequence of a T-cell-derived lymphokine with growth factor activity for B-cell hybridomas.Proceedings of the National Academy of Sciences, 1986
- Antiglucocorticoid effects of endotoxin.1984