The role of NOS3 expression and action in DN is controversial; therefore although low or lack of NOS3 has been shown to exacerbate DN (Wang et al., 2011; Zhao et al., 2006), a recent publication (Natarajan et al., 2019) showed that overexpression of NOS3 in Ins2Akita mice exacerbates DN probably via increased NOS3 uncoupling and oxidative stress rather than by increased renal NO production/action. Here, NOS3 is linked to liver dysplastic nodule.