Impaired insulin secretion and insulin resistance are the primary characteristics of type 2 diabetes (T2D). However, the mechanisms underlying insulin secretion failure have yet to be elucidated. The present study demonstrated that sirtuin 5 (SIRT5) is upregulated in patients with T2D and in pancreatic β-cell lines. It was also revealed that elevated SIRT5 expression is positively associated with age and blood glucose levels, and negatively associated with pancreatic and duodenal homeobox 1 (PDX1) expression. Colony formation and Cell Counting Kit-8 assays demonstrated that SIRT5 suppressed the proliferation of pancreatic β-cells in vitro. In addition, downregulation of SIRT5 promoted the secretion of insulin. Additionally, SIRT5 ectopic expression downregulated the expression of PDX1 and the inhibition of SIRT5 upregulated PDX1 expression. Chromatin immunoprecipitation assay analysis demonstrated that SIRT5 may regulate the transcription of PDX1 via H4K16 deacetylation. In conclusion, the results of the present study indicate that SIRT5 may serve an important role in the pathogenesis of T2D, and may present a novel therapeutic target for the treatment of patients with T2D.
Keywords: insulin secretion; pancreatic and duodenal homeobox 1; proliferation; sirtuin 5; type 2 diabetes.