A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism

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A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism

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Title: A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism
Author: Herman, Mark Andrew; Peroni, Odile Daniele; Villoria, Jorge; Schön, Michael R.; Abumrad, Nada A.; Blüher, Matthias; Klein, Samuel; Kahn, Barbara

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Citation: Herman, Mark A., Odile D. Peroni, Jorge Villoria, Michael R. Schön, Nada A. Abumrad, Matthias Blüher, Samuel Klein, and Barbara B. Kahn. 2012. A novel chREBP isoform in adipose tissue regulates systemic glucose metabolism. Nature 484(7394): 333-338.
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Abstract: The prevalence of obesity and type 2-diabetes is increasing worldwide and threatens to shorten lifespan. Impaired insulin action in peripheral tissues is a major pathogenic factor. Insulin stimulates glucose uptake in adipose tissue through the Glut4-glucose transporter and alterations in adipose-Glut4 expression or function regulate systemic insulin sensitivity. Downregulation of adipose tissue-Glut4 occurs early in diabetes development. Here we report that adipose tissue-Glut4 regulates the expression of carbohydrate responsive-element binding protein (ChREBP), a transcriptional regulator of lipogenic and glycolytic genes. Furthermore, adipose-ChREBP is a major determinant of adipose tissue fatty acid synthesis and systemic insulin sensitivity. We discovered a new mechanism for glucose-regulation of ChREBP: Glucose-mediated activation of the canonical ChREBP isoform (ChREBPα) induces expression of a novel, potent isoform (ChREBPβ) that is transcribed from an alternative promoter. ChREBPβ expression in human adipose tissue predicts insulin sensitivity indicating that it may be an effective target for treating diabetes.
Published Version: doi:10.1038/nature10986
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341994/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10531921
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