Experiments in two pancreatic β-cell lines (MIN6 and INS-1) suggest that SIRT5 inhibition facilitated pancreatic β-cell proliferation and insulin secretion.350 Moreover, SIRT5 negatively regulates the transcription of PDX1 through its deacetylase activity,350 and subsequently, the downregulation of PDX1 expression aggravates DM.838,839 These studies suggest that high expression of SIRT3, SIRT4, and SIRT6 and low expression of SIRT5 might exert protective effects on the development of DM. This evidence concerns the gene SIRT4 and diabetes mellitus.