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.
Keywords: Reactive oxygen species, type 2 diabetes mellitus, Nrf2, antioxidant, MAP kinase, PI3K/Akt., insulin resistance, β-cell dysfunction, GSIS, Redox homeostasis, PPARγ, PGC1α, insulin sensitivity
Mini-Reviews in Medicinal Chemistry
Title: ROS Acts as a Double-Edged Sword in the Pathogenesis of Type 2 Diabetes Mellitus: Is Nrf2 a Potential Target for the Treatment?
Volume: 11 Issue: 12
Author(s): X. Wang and C. X. Hai
Affiliation:
Keywords: Reactive oxygen species, type 2 diabetes mellitus, Nrf2, antioxidant, MAP kinase, PI3K/Akt., insulin resistance, β-cell dysfunction, GSIS, Redox homeostasis, PPARγ, PGC1α, insulin sensitivity
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.
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Wang X. and X. Hai C., ROS Acts as a Double-Edged Sword in the Pathogenesis of Type 2 Diabetes Mellitus: Is Nrf2 a Potential Target for the Treatment?, Mini-Reviews in Medicinal Chemistry 2011; 11 (12) . https://dx.doi.org/10.2174/138955711797247761
DOI https://dx.doi.org/10.2174/138955711797247761 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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