title: The role of oxidative stress in the pathogenesis of type 2 diabetes: from molecular mechanism to clinical implication.
abstract: A surplus of food supply has evoked a worldwide increase in incidence of type 2 diabetes. This trend will have a significant impact on the life span of people living in modern societies. In contrast, reduced calorie intake has significant impact on preventing type 2 diabetes and increasing longevity. Increased production of reactive oxygen species (ROS), resulting in oxidative stress, has long been proposed as a unifying mechanism linking nutrient excess and diabetes. This review describes the updated mechanism by which oxidative stress provoked by nutrient excess contributes to the development of insulin resistance and pancreatic betacell failure. However, despite the promising results in cellular and animal models, major clinical trials have failed to demonstrate beneficial effect of antioxidants on the prevention of type 2 diabetes or the degree of glycemic control in individuals with diabetes. Emerging evidence shows that ROS also function as an insulin-signaling molecule in normal physiology and casts doubt on the potential beneficial effect of antioxidants. The gap between basic research and clinical outcomes heightens the importance for elucidating the precise molecular mechanisms by which cellular redox status affects insulin signaling.
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan; Department of Internal Medicine, National TaiwanUniversity Hospital, Taipei, Taiwan.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Chang
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Chuang