Nitric Oxide, Oxidative Stress, and Interplay in Diabetic Endothelial Dysfunction

Figure 2

eNOS uncoupling in diabetes mellitus. Diabetes and insulin resistance are associated with eNOS uncoupling due to decreased levels of BH₄. eNOS uncoupling leads to the production of superoxide anion (O₂⁻), rather than NO. Superoxide, in turn, is dismutated to H₂O₂ or reacts with NO, leading to the formation of peroxynitrite (ONOO⁻) and to a further it decreases NO bioavailability. Increased ONOO⁻ and H₂O₂ levels induce oxidative stress that further aggravates BH₄ depauperation.