Peroxynitrite-Driven Mechanisms in Diabetes and Insulin Resistance – the Latest Advances

K.      Stadler

doi:10.2174/092986711794088317

Abstract

Since its discovery, peroxynitrite has been known as a potent oxidant in biological systems, and a rapidly growing body of literature has characterized its biochemistry and role in the pathophysiology of various conditions. Either directly or by inducing free radical pathways, peroxynitrite damages vital biomolecules such as DNA, proteins including enzymes with important functions, and lipids. It also initiates diverse reactions leading eventually to disrupted cell signaling, cell death, and apoptosis. The potential role and contribution of this deleterious species has been the subject of investigation in several important diseases, including but not limited to, cancer, neurodegeneration, stroke, inflammatory conditions, cardiovascular problems, and diabetes mellitus. Diabetes, obesity, insulin resistance, and diabetes-related complications represent a major health problem at epidemic levels. Therefore, tremendous efforts have been put into investigation of the molecular basics of peroxynitrite-related mechanisms in diabetes. Studies constantly seek new therapeutical approaches in order to eliminate or decrease the level of peroxynitrite, or to interfere with its downstream mechanisms. This review is intended to emphasize the latest findings about peroxynitrite and diabetes, and, in addition, to discuss recent and novel advances that are likely to contribute to a better understanding of peroxynitrite-mediated damage in this disease.

Keywords: Diabetes, diabetic complications, insulin resistance, lipid peroxidation, nitrotyrosine, peroxynitrite, neurodegenerative disorders, superoxide dismutases, tryptophanes, cardiomyopathy, nephropathy, retinopathy, juvenile, hyperglycemia, streptozotocin, hypoalgesia, N-(3-(Aminomethyl)benzyl)acetamidine, insulin receptor substrate -1, molsidomine