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ROS acts as a double-edged sword in the pathogenesis of type 2 diabetes mellitus: is Nrf2 a potential target for the

X Wang1, C X Hai

  • 1Department of Toxicology, School of Preventive Medicine, The Fourth Military Medical University, Xi'an, Shaanxi, P. R. China.

Mini Reviews in Medicinal Chemistry
|August 25, 2011
PubMed

Insights

Reactive oxygen species (ROS) play a dual role in type 2 diabetes (T2DM). Targeting the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway offers a promising therapeutic strategy for T2DM.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Endocrinology

Background:

  • Reactive oxygen species (ROS) are implicated in type 2 diabetes mellitus (T2DM) pathogenesis, contributing to insulin resistance and beta-cell dysfunction.
  • However, ROS also play essential roles in normal insulin signaling and glucose-stimulated insulin secretion (GSIS), necessitating a nuanced understanding of their physiological and pathological functions.
  • Redox homeostasis is regulated by the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), with its dysregulation linked to diabetes development.

Purpose of the Study:

  • To explore the complex role of ROS in T2DM.
  • To investigate the involvement of Nrf2 in regulating antioxidant defenses and its connection to diabetes.
  • To evaluate Nrf2 as a potential therapeutic target for T2DM.

Main Methods:

  • Review of existing literature on ROS, Nrf2, and T2DM.
  • Analysis of cross-talk between Nrf2 and key signaling pathways (e.g., PPARγ, PGC1α, PI3K/Akt).
  • Evaluation of Nrf2's role in cellular response to oxidative stress.

Main Results:

  • ROS contribute to both the development and normal functioning of insulin signaling in T2DM.
  • Nrf2 interacts with critical pathways involved in antioxidant defense and metabolic regulation.
  • Nrf2 appears to be a key determinant of cell survival under oxidative stress.

Conclusions:

  • Modulating Nrf2 levels can enhance GSIS and insulin sensitivity, presenting a potential therapeutic strategy for T2DM.
  • Nrf2 represents a promising molecular target for the development of novel T2DM treatments.

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