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.
Export Options
About this article
Cite this article as:
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 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
High-Density Lipoprotein at the Interface of Type 2 Diabetes Mellitus And Cardiovascular Disorders
Current Pharmaceutical Design Periodontal Regenerative Materials and Their Applications: Goodness of Fit?
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Role of Connexins and Pannexins in Ischemic Stroke
Current Medicinal Chemistry Cardiovascular Disease in Juvenile Idiopathic Arthritis
Current Vascular Pharmacology Nmr Studies Of The Prionogenic Peptide Derived From Sup35 Protein
Protein & Peptide Letters Ganoderma lucidum: A Potent Pharmacological Macrofungus
Current Pharmaceutical Biotechnology Which Dose of Folic Acid Should Pregnant Diabetic Women Receive?
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Demographic and Clinical Evaluation of Patients with Pancreatic Cancer in Mashhad University of Medical Sciences During 2002-2013
Current Cancer Therapy Reviews Validation of Neuropad in the Assessment of Peripheral Diabetic Neuropathy in Patients with Diabetes Mellitus Versus the Michigan Neuropathy Screening Instrument, 10g Monofilament Application and Biothesiometer Measurement
Current Vascular Pharmacology Therapeutic Strategies for Treatment of Inflammation-related Depression
Current Neuropharmacology Anthropometric Correlation with Metabolic Syndrome in Sarajevo Population
Endocrine, Metabolic & Immune Disorders - Drug Targets From Brain Ischemia-Reperfusion Injury to Possible Sporadic Alzheimers Disease
Current Neurovascular Research Can Statins Prevent Progression of Degenerated Aortic Valve Stenosis?
Vascular Disease Prevention (Discontinued) The Utility of Metformin Therapy in Reproductive-Aged Women with Polycystic Ovary Syndrome (PCOS)
Current Pharmaceutical Biotechnology The Metabolite Trimethylamine-N-Oxide is an Emergent Biomarker of Human Health
Current Medicinal Chemistry Charcot Neuroarthropathy: From the Laboratory to the Bedside
Current Diabetes Reviews Prevalence of Latent Tuberculosis (LTB) Among Pregnant Women in a High Burden Setting in Sudan using Interferon Gamma (IFN- γ) Releasing Assay (IGRA)
Current Women`s Health Reviews Targeting Farnesoid-X-Receptor: From Medicinal Chemistry to Disease Treatment
Current Medicinal Chemistry Established and In-trial GPCR Families in Clinical Trials: A Review for Target Selection
Current Drug Targets Endocannabinoid Receptor Antagonists and Other Emerging Pharmacological Strategies for Weight Reduction
Current Drug Targets - Cardiovascular & Hematological Disorders