Intertwined Role of Reactive Oxygen, Nitrogen and Carbon in Diabetic State

Diabetes is a metabolic disorder of multiple etiologies, characterized by chronic hyperglycemia caused by defects in the secretion of insulin or the action of insulin, or both. Production of reactive oxygen species (ROS) and lipid peroxidation are increased in diabetic patients, especially in those with poor glycemic control. An increase in steady-state level of reactive oxygen species (ROS) or reactive carbonyl species (RCS) may result in so-called “oxidative stress” or “carbonyl stress”, respectively. Reactive nitrogen species (RNS) is also a subset of ROS. ROS and RNS include hydroxyl radical (•OH), hydrogen peroxide (H2O2), superoxide (O2), nitric oxide (NO•), peroxynitrite (ONOO−). In physiological conditions, mitochondria are the major site of intracellular ROS production, due to electron leakage along the respiratory chain. Protein kinase C also becomes activated in retinal endothelial cells under hyperglycemic conditions and can lead to activation of NADH oxidase. Metal-catalyzed auto oxidation of reducing carbohydrates could be involved in the formation of AGEs and ROS. Hexosamine biosynthesis pathway is an additional pathway of glucose metabolism that may mediate some of the toxic effects of glucose Oxidized lipoproteins activate inflammatory signaling, which in turn aggravates the inflammation. Therefore, clearance of oxidative and nitrosative stress and inhibition of inflammation have been considered good strategies for the treatment of diabetic complications.