SIRT2 ablation inhibits glucose-stimulated insulin secretion through decreasing glycolytic flux.

ABSTRACT: Rationale: Sirtuins are NAD⁺-dependent protein deacylases known to have protective effects against age-related diseases such as diabetes, cancer, and neurodegenerative disease. SIRT2 is the only primarily cytoplasmic isoform and its overall role in glucose homeostasis remains uncertain. Methods: SIRT2-knockout (KO) rats were constructed to evaluate the role of SIRT2 in glucose homeostasis. The effect of SIRT2 on β-cell function was detected by investigating the morphology, insulin secretion, and metabolomic state of islets. The deacetylation and stabilization of GKRP in β-cells by SIRT2 were determined by western blot, adenoviral infection, and immunoprecipitation. Results: SIRT2-KO rats exhibited impaired glucose tolerance and glucose-stimulated insulin sec

SUBMITTER: Zhou F 

PROVIDER: S-EPMC7978320 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature