Feedback regulation of hepatic gluconeogenesis through modulation of SHP/Nr0b2 gene expression by Sirt1 and FoxO1.

ABSTRACT: Protein deacetylase Sirt1 has been implicated in the regulation of hepatic gluconeogenesis; however, the mechanisms are not fully understood. To further elucidate how Sirt1 regulates gluconeogenesis, we took a loss-of-function approach by deleting the coding DNA sequence for the catalytic domain of the Sirt1 gene in the liver of a wild-type mouse (LKO(Sirt)¹) or a genetic diabetic mouse in which hepatic insulin receptor substrates 1 and 2 are deleted (DKO(Irs½)). Whereas LKO(Sirt)¹ mice exhibited normal levels of fasting and fed blood glucose, inactivation of Sirt1 in DKO(Irs½) mice (TKO(Irs½:Sirt)¹) reduced blood glucose levels and moderately improved systemic glucose tolerance. Pyruvate tolerance was also significantly improved in TKO(Irs½:Sirt)¹ mice, suggesting that Sirt1 promotes hepa

SUBMITTER: Wei D 

PROVIDER: S-EPMC3043623 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature