Back to Search
Start Over
The Histone Deacetylase Sirt6 Regulates Glucose Homeostasis via Hif1α
- Source :
-
Cell . Jan2010, Vol. 140 Issue 2, p280-293. 14p. - Publication Year :
- 2010
-
Abstract
- Summary: SIRT6 is a member of a highly conserved family of NAD+-dependent deacetylases with various roles in metabolism, stress resistance, and life span. SIRT6-deficient mice develop normally but succumb to a lethal hypoglycemia early in life; however, the mechanism underlying this hypoglycemia remained unclear. Here, we demonstrate that SIRT6 functions as a histone H3K9 deacetylase to control the expression of multiple glycolytic genes. Specifically, SIRT6 appears to function as a corepressor of the transcription factor Hif1α, a critical regulator of nutrient stress responses. Consistent with this notion, SIRT6-deficient cells exhibit increased Hif1α activity and show increased glucose uptake with upregulation of glycolysis and diminished mitochondrial respiration. Our studies uncover a role for the chromatin factor SIRT6 as a master regulator of glucose homeostasis and may provide the basis for novel therapeutic approaches against metabolic diseases, such as diabetes and obesity. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00928674
- Volume :
- 140
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 58638461
- Full Text :
- https://doi.org/10.1016/j.cell.2009.12.041