Abstract
Abnormal nitric oxide (NO) metabolism has been associated with the development of insulin resistance and type 2 diabetes (T2D). The concept of NO deficiency is supported by human studies on polymorphisms of endothelial NO synthase (eNOS) gene, animal knockout models for NO synthase isoforms (NOSs), and pharmacological evidence, showing detrimental effects of NOS inhibitors and salutary effects of NO donors on carbohydrate metabolism. On the other hand, T2D and insulin resistance may impair NO homeostasis due to hyperglycemia, oxidative stress, and inflammation. Reduced production of NO [i.e., impaired L-arginine-NOS pathway and function of the nitrate (NO3)-nitrite (NO2)-NO pathway], impaired NO transport within the circulation and delivery to target cells, as well as disrupted NO signaling (e.g., via oxidative-induced NO quenching, and impaired NO-cGMP signaling pathway) can all lead to a reduced NO bioactivity in T2D. This chapter focuses on the role of impaired NO metabolism in T2D.