Age-associated loss of Sirt1-mediated enhancement of glucose-stimulated insulin secretion in beta cell-specific Sirt1-overexpressing (BESTO) mice.

ABSTRACT: The Sir2 (silent information regulator 2) family of NAD-dependent deacetylases regulates aging and longevity across a wide variety of organisms, including yeast, worms, and flies. In mammals, the Sir2 ortholog Sirt1 promotes fat mobilization, fatty acid oxidation, glucose production, and insulin secretion in response to nutrient availability. We previously reported that an increased dosage of Sirt1 in pancreatic beta cells enhances glucose-stimulated insulin secretion (GSIS) and improves glucose tolerance in beta cell-specific Sirt1-overexpressing (BESTO) transgenic mice at 3 and 8 months of age. Here, we report that as this same cohort of BESTO mice reaches 18-24 months of age, the GSIS regulated by Sirt1 through repression of Ucp2 is blunted. Increased body weight and hyperlipidemia alon

SUBMITTER: Ramsey KM 

PROVIDER: S-EPMC2238677 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature