ROS acts as a double-edged sword in the pathogenesis of type 2 diabetes mellitus: is Nrf2 a potential target for the treatment?
ROS acts as a double-edged sword in the pathogenesis of type 2 diabetes mellitus: is Nrf2 a potential target for the treatment?
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DOI：
10.2174/138955711797247761
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发表时间：
2011-09
期刊：
影响因子：
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通讯作者：
X. Wang;C. Hai
中科院分区：
文献类型：
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作者：
X. Wang;C. Hai
尽管T2 DM的发病机制尚不清楚，但已证实多种来源的活性氧（ROS）在多种类型的胰岛素抵抗中起着重要作用，并导致β细胞功能障碍，从而促进T2 DM的发生和发展。但令人不解的是，有害的ROS在β细胞正常的胰岛素信号转导和葡萄糖刺激的胰岛素分泌（GSIS）中也起着重要作用，这迫使我们从更广泛的角度重新认识ROS在生理和病理条件下的作用。氧化还原稳态受转录因子核因子红细胞2相关因子2（Nrf 2）的严格控制，其异常被认为与糖尿病有关。越来越多的证据表明，Nrf 2与PPARγ、PGC 1 α、PI 3 K/Akt在调节抗氧化酶和糖尿病的发生发展中有重要的交互作用。因此，这些证据表明，当细胞暴露于氧化剂环境时，Nrf 2可能是做出生存和死亡决定的关键因素。总之，通过调节Nrf 2水平来增强GSIS和胰岛素敏感性是开发新疗法的潜在途径。Nrf 2可能成为治疗T2 DM的一个有前景的靶点。
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.