title: ROS acts as a double-edged sword in the pathogenesis of type 2 diabetes mellitus: is Nrf2 a potential target for the treatment?
abstract: Although the clear mechanism of T2DM is still to be elucidated, it has been well established that reactive oxygen species (ROS) derived from multiple sources plays a causal role in multiple types of insulin resistance and contributes to β-cell dysfunction thus enhances the development and progression of T2DM. What is incomprehensible is that the detrimental ROS also plays a substantial role in the normal insulin signal transduction and glucose-stimulated insulin secretion (GSIS) in β-cell, which forces us to re-recognize the role of ROS under physiological and pathological conditions in a more broad way. Redox homeostasis is tightly controlled by the transcriptional factor nuclear factor erythroid 2-related factor 2 (Nrf2), whose abnormality is believed to be related with diabetes. Accumulating evidences suggest that there are important cross-talks between Nrf2 and PPARγ, PGC1α, PI3K/Akt on regulating antioxidant enzymes and the development of diabetes. Therefore, these evidences indicate that Nrf2 may be a critical element in taking survival and death decisions when cells are exposed to an oxidant environment. In conclusion, enhancing GSIS and insulin sensitivity through the regulation of Nrf2 levels is a potential avenue for developing new therapeutics. Nrf2 may become a promising target for the treatment of T2DM.
authors.affiliation: Department of Toxicology, School of Preventive Medicine, The Fourth Military Medical University, Xi'an, Shaanxi, P. R. China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: C X
authors.initials: CX
authors.lastname: Hai
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000639:trends*; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species