Evidence for an indirect transcriptional regulation of glucose-6-phosphatase gene expression by liver X receptors
- Department of Medical Biochemistry and Molecular Biology, University of Greifswald, D-17487 Greifswald (Germany)
- Department of Biosciences at NOVUM, Karolinska Institute (Sweden)
- Department of Endocrinology, Diabetes and Rheumatology, University of Duesseldorf, D-40225 Duesseldorf (Germany)
- Aventis Pharma, TD Metabolism, Bldg. H825, D-65926 Frankfurt/Main (Germany)
Liver X receptor (LXR) paralogues {alpha} and {beta} (LXR{alpha} and LXR{beta}) are members of the nuclear hormone receptor family and have oxysterols as endogenous ligands. LXR activation reduces hepatic glucose production in vivo through the inhibition of transcription of the key gluconeogenic enzymes phosphoenolpyruvate carboxykinase and glucose-6-phosphatase (G6Pase). In the present study, we investigated the molecular mechanisms involved in the regulation of G6Pase gene expression by LXR. Both T0901317, a synthetic LXR agonist, and the adenoviral overexpression of either LXR{alpha} or LXR{beta} suppressed G6Pase gene expression in H4IIE hepatoma cells. However, compared to the suppression of G6Pase expression seen by insulin, the decrease of G6Pase mRNA by LXR activation was delayed and was blocked by cycloheximide, an inhibitor of protein synthesis. These observations, together with the absence of a conserved LXR-binding element within the G6Pase promoter, suggest an indirect inhibition of G6Pase gene expression by liver X receptors.
- OSTI ID:
- 20793224
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 338, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2005.10.030; PII: S0006-291X(05)02277-1; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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