A study on endothelial cells from type 2 diabetes mellitus (T2DM) mice found that exogenous irisin reduced endothelial protection by inhibiting the activation of the protein kinase C-β (PKC-β)/NADPH oxidase and NF-κB/Inducible nitric oxide synthase (iNOS) pathway, and the reduced levels of ONOO— to decrease oxidative/nitrative stress, thereby achieving endothelial protection [60]. This evidence concerns the gene NOS2 and type 2 diabetes mellitus.