Diabetes and oxidative stress: Dipeptidyl peptidase-4 inhibitors

Abstract

Diabetes mellitus is one of the commonmetabolic diseases increasing the mortality worldwide. As predicted by the World Health Organization, the number of people suffering from these diseases is rapidly increasing. Two important factors in the progression of the disease are obesity and reduced physical activity. The greatest cause of death among diabetic patients is the cardiovascular complications caused by the microvascular and macrovascular dysfunctions. Clinical studies and experimental evidence suggest that oxidative stress plays an important role in the pathophysiology of diabetes mellitus. Free radicals in diabetes are produced by oxidation of glucose, non-enzymaticglycation of proteins, and subsequent oxidative damage of glycosylated proteins and other macromolecules. High levels of free radicals and lipid peroxidation and malfunction of antioxidant defense mechanisms cause cell damage in various organs, leading to insulin resistance and other diabetes mellitus complications. Several studies have pointed the role of antioxidant therapy in diabetes. Dipeptidyl peptidase-4(DPP-4) inhibitors inhibit the degradation of incretin hormones by DPP-4 membrane-bound enzyme and play an important role in glucose homeostasis and insulin secretion. These inhibitors are new candidates for the treatment of diabetes. This study is aimed to review the roles of changes in biomarkers of oxidative stress and antioxidant defense systems in the progression of diabetes, and the antioxidative roles of DPP-4 inhibitors in the prevention of diabetic complications.