SIRT1 and diabetes mellitus: Moreover, SirT1 inhibits the mitochondrial adaptor protein p66Shc, a critical modulator of intracellular redox state and a major contributor of oxidative damage-induced endothelial dysfunction in the settings of diabetes (Zhou et al., 2011; Paneni et al., 2013), by directly deacetylating its lysine 81 (Kumar et al., 2017).