Diabetes or hyperglycemia-mediated overgeneration of superoxide anions and MG formation results in decreased expression of eNOS, epigenetic changes and GLUT4 suppression, as well as suppressed Nrf2 transcriptional activity and increased NFκB p65 activity, subsequently triggering oxidative stress, inflammation, vascular dysfunction and glucose intolerance. Here, NOS3 is linked to diabetes mellitus.