Trends Mol Med. 2005 Jun;11(6):262-5.

Does chasing selected 'Fox' to the nucleus prevent diabetes?

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Department of Cell Physiology and Metabolism, University Medical Center, CH-1211 Geneva 4, Switzerland. Haiyan.Wang@medicine.unige.ch

Abstract

Foxa2 (Hnf3beta) is a winged-helix/forkhead transcription factor that regulates gene expression in the liver, pancreatic islets and adipocytes. It is required for the maintenance of glucose and lipid homeostasis. Hyperinsulinemia-mediated inactivation of Foxa2 by nuclear exclusion has recently been implicated in the development of liver steatosis and insulin resistance in three animal models of diabetes. These abnormalities were cured by adenovirus-mediated expression of a constitutively active form of Foxa2 containing a mutated T156 phosphorylation site, which increases fatty acid oxidation and reduces its biosynthesis. Accordingly, the prevention of phosphorylation of Foxa2 was suggested as a pharmacological target for the treatment of obesity and diabetes.

PMID:: 15949766; [PubMed - indexed for MEDLINE]

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Foxa2 regulates lipid metabolism and ketogenesis in the liver during fasting and in diabetes. [Nature. 2004]
Foxa2 regulates lipid metabolism and ketogenesis in the liver during fasting and in diabetes.
Wolfrum C, Asilmaz E, Luca E, Friedman JM, Stoffel M. Nature. 2004 Dec 23; 432(7020):1027-32.
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Cited by 3 PubMed Central articles

Foxa1 reduces lipid accumulation in human hepatocytes and is down-regulated in nonalcoholic fatty liver. [PLoS One. 2012]
Foxa1 reduces lipid accumulation in human hepatocytes and is down-regulated in nonalcoholic fatty liver.
Moya M, Benet M, Guzmán C, Tolosa L, García-Monzón C, Pareja E, Castell JV, Jover R. PLoS One. 2012; 7(1):e30014. Epub 2012 Jan 6.
Nuclear pregnane X receptor cross-talk with FoxA2 to mediate drug-induced regulation of lipid metabolism in fasting mouse liver. [J Biol Chem. 2007]
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Nakamura K, Moore R, Negishi M, Sueyoshi T. J Biol Chem. 2007 Mar 30; 282(13):9768-76. Epub 2007 Jan 30.
Review In control of biology: of mice, men and Foxes. [Biochem J. 2006]
Review In control of biology: of mice, men and Foxes.
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