Diabetic peripheral neuropathy: Role of nitric oxide.

Abstract

Diabetic peripheral neuropathy (DPN) is one of the most prevalent long-term complications in type 1 (T1DM) and type 2 (T2DM) diabetes mellitus and is characterized by structural (microangiopathy, axonal atrophy, impaired myelination, and disrupted Schwann cell-axon interactions) and functional (impaired axonal transport and sensory and motor disorders) changes in neurons. Nitric oxide (NO) contributes to the development and progression of DPN as it has a role in the perfusion and electrophysiological functions of neurons. NO is essential for sustaining nerve conduction velocity (NCV) through modulation of Na⁺/K⁺-ATPase activity. Isoform-specific alterations in NO synthase (NOS) expression and activity occur during the development of DPN. Neural NOS (nNOS) generally exhibits consistent downregulation, especially in T2DM models, whereas inducible NOS (iNOS) tends to be upregulated in the T1DM model. NO has been proposed as a potential therapeutic agent for DPN because of its potent vasodilatory effects. NO-donating derivatives (e.g., NCX1404, PRG150) have demonstrated both symptomatic and disease-modifying effects in DPN. In conclusion, NO plays a role in the pathophysiology of DPN and is a therapeutic target for managing neuropathy in diabetes.