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 Hif1alpha, a critical 
regulator of nutrient stress responses. Consistent with this notion, 
SIRT6-deficient cells exhibit increased Hif1alpha 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.