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
-
Natural Products as Farnesoid X Receptor (FXR) Agonists: Their Interactions with FXR Ligand Binding Region
Mini-Reviews in Organic Chemistry The Effect of Antihypertensive Agents on Insulin Sensitivity, Lipids and Haemostasis
Current Vascular Pharmacology FoxO3a Governs Early Microglial Proliferation and Employs Mitochondrial Depolarization with Caspase 3, 8, and 9 Cleavage During Oxidant Induced Apoptosis
Current Neurovascular Research Is there a Role for Oral Triple Therapy in Patients with Acute Coronary Syndromes Without Atrial Fibrillation?
Current Vascular Pharmacology Diabetogenic Effects of Parthinium hysterophorous Induced Allergic Rhinitis
Inflammation & Allergy - Drug Targets (Discontinued) IGF-I Abuse in Sport
Current Drug Abuse Reviews Hypertension in Type 2 Diabetes Mellitus: Do We Need to Redefine the Role of Sulfonylureas?
Recent Advances in Cardiovascular Drug Discovery (Discontinued) Novel Non-rodent Models of Kidney Disease
Current Molecular Medicine SGLT-2 Inhibition: Novel Therapeutics for Reno-and Cardioprotection in Diabetes Mellitus
Current Diabetes Reviews Angiotensin-Converting Enzyme Inhibitors in Veterinary Medicine
Current Pharmaceutical Design Challenges with Insulin Use Among Patients with Type 2 Diabetes Mellitus: Focus on a Tertiary Healthcare Setting in South-East Nigeria
Current Diabetes Reviews Refining Genetic Approaches for Identifying Behavioral Loci
Current Genomics Tardive Dyskinesia with Atypical Antipsychotic Drugs
Current Drug Therapy Cardio-protective Effects of Glucagon-like Peptide-1 Receptor Agonists: An Overview of Systematic Reviews and Publication Overlap
Current Pharmaceutical Design Proteins of the Esterase Family: Patents for Some Proteins in Search of Metabolic Functions
Recent Patents on Biomarkers Antithrombotic Treatment in Diabetes Mellitus: A Review of the Literature about Antiplatelet and Anticoagulation Strategies Used for Diabetic Patients in Primary and Secondary Prevention
Current Pharmaceutical Design Glucocorticoids in Pregnancy
Current Pharmaceutical Biotechnology Fetal Protein Restriction, Taurine and Islet Plasticity
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Therapeutic Implications of Beta-Adrenergic Receptor Pharmacodynamic Properties
Current Clinical Pharmacology Meet Our Editorial Board Member
Current Diabetes Reviews