Bhatti, Jasvinder SinghSehrawat, AbhishekMishra, JayapriyaSidhu, Inderpal SinghNavik, UmashankerKhullar, NainaKumar, ShashankBhatti, Gurjit KaurReddy, P. Hemachandra2024-01-212024-08-142024-01-212024-08-142022-04-07891584910.1016/j.freeradbiomed.2022.03.019http://10.2.3.109/handle/32116/4209Type 2 diabetes (T2DM) is a persistent metabolic disorder rising rapidly worldwide. It is characterized by pancreatic insulin resistance and ?-cell dysfunction. Hyperglycemia induced reactive oxygen species (ROS) production and oxidative stress are correlated with the pathogenesis and progression of this metabolic disease. To counteract the harmful effects of ROS, endogenous antioxidants of the body or exogenous antioxidants neutralise it and maintain bodily homeostasis. Under hyperglycemic conditions, the imbalance between the cellular antioxidant system and ROS production results in oxidative stress, which subsequently results in the development of diabetes. These ROS are produced in the endoplasmic reticulum, phagocytic cells and peroxisomes, with the mitochondrial electron transport chain (ETC) playing a pivotal role. The exacerbated ROS production can directly cause structural and functional modifications in proteins, lipids and nucleic acids. It also modulates several intracellular signaling pathways that lead to insulin resistance and impairment of ?-cell function. In addition, the hyperglycemia-induced ROS production contributes to micro- and macro-vascular diabetic complications. Various in-vivo and in-vitro studies have demonstrated the anti-oxidative effects of natural products and their derived bioactive compounds. However, there is conflicting clinical evidence on the beneficial effects of these antioxidant therapies in diabetes prevention. This review article focused on the multifaceted role of oxidative stress caused by ROS overproduction in diabetes and related complications and possible antioxidative therapeutic strategies targeting ROS in this disease. � 2022 Elsevier Inc.en-USAntioxidant enzymesElectron transport systemHyperglycemiaInsulin resistanceOxidative stressPancreatic ?-cellsReactive oxygen speciesReviewhttps://linkinghub.elsevier.com/retrieve/pii/S0891584922001228