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A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism
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-Gl...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341994/ https://www.ncbi.nlm.nih.gov/pubmed/22466288 http://dx.doi.org/10.1038/nature10986 |
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author | Herman, Mark A. Peroni, Odile D. Villoria, Jorge Schön, Michael R. Abumrad, Nada A. Blüher, Matthias Klein, Samuel Kahn, Barbara B. |
author_facet | Herman, Mark A. Peroni, Odile D. Villoria, Jorge Schön, Michael R. Abumrad, Nada A. Blüher, Matthias Klein, Samuel Kahn, Barbara B. |
author_sort | Herman, Mark A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3341994 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
record_format | MEDLINE/PubMed |
spelling | pubmed-33419942012-10-19 A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism Herman, Mark A. Peroni, Odile D. Villoria, Jorge Schön, Michael R. Abumrad, Nada A. Blüher, Matthias Klein, Samuel Kahn, Barbara B. Nature Article 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. 2012-04-19 /pmc/articles/PMC3341994/ /pubmed/22466288 http://dx.doi.org/10.1038/nature10986 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Herman, Mark A. Peroni, Odile D. Villoria, Jorge Schön, Michael R. Abumrad, Nada A. Blüher, Matthias Klein, Samuel Kahn, Barbara B. A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism |
title | A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism |
title_full | A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism |
title_fullStr | A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism |
title_full_unstemmed | A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism |
title_short | A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism |
title_sort | novel chrebp isoform in adipose tissue regulates systemic glucose metabolism |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341994/ https://www.ncbi.nlm.nih.gov/pubmed/22466288 http://dx.doi.org/10.1038/nature10986 |
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