Abstract
Both protein kinase C (PKC) activation and increased oxidative stress have been paid attention to as important causative factors for diabetic vascular complications. In this article, we show a PKC-dependent increase in oxidative stress in vascular tissues of diabetes and insulin resistant state. High glucose level and free fatty acids stimulate de novo diacylglycerol (DAG)-PKC pathway and subsequently stimulate reactive oxygen species (ROS) production through a PKC-dependent activation of NAD(P)H oxidase. Increasing evidence has also shown that NAD(P)H oxidase components are upregulated in micro- and macro- vascular tissues of animal models and patients of diabetes and obesity. It is also noted that increased intrinsic angiotensin II production may amplify such a PKC-dependent activation of NAD(P)H oxidase in diabetic vascular tissues. These mechanisms may play an important role in the diabetic vascular complications and the accelerated atherosclerosis associated with diabetes and obesity. In addition, recent reports have shown that NAD(P)H oxidases exist in pancreatic β-cells and adipocytes, and this oxidase-generated ROS production may play an important role in both the progressive β-cell dysfunction and the dysregulated adipocytokine production and subsequent obesity-induced metabolic syndrome. These results suggest that an NAD(P)H oxidase activation may be a useful therapeutic target for preventing diabetic vascular complications, progressive β-cell dysfunction and metabolic syndrome.
Keywords: nad(p)h oxidase, oxidative stress, protein kinase c, diabetic complications, atherosclerosis, cell, adipocyte, metabolic syndrome
Current Drug Targets
Title: NAD(P)H Oxidase Activation: A Potential Target Mechanism for Diabetic Vascular Complications, Progressive β-Cell Dysfunction and Metabolic Syndrome
Volume: 6 Issue: 4
Author(s): Toyoshi Inoguchi and Hajime Nawata
Affiliation:
Keywords: nad(p)h oxidase, oxidative stress, protein kinase c, diabetic complications, atherosclerosis, cell, adipocyte, metabolic syndrome
Abstract: Both protein kinase C (PKC) activation and increased oxidative stress have been paid attention to as important causative factors for diabetic vascular complications. In this article, we show a PKC-dependent increase in oxidative stress in vascular tissues of diabetes and insulin resistant state. High glucose level and free fatty acids stimulate de novo diacylglycerol (DAG)-PKC pathway and subsequently stimulate reactive oxygen species (ROS) production through a PKC-dependent activation of NAD(P)H oxidase. Increasing evidence has also shown that NAD(P)H oxidase components are upregulated in micro- and macro- vascular tissues of animal models and patients of diabetes and obesity. It is also noted that increased intrinsic angiotensin II production may amplify such a PKC-dependent activation of NAD(P)H oxidase in diabetic vascular tissues. These mechanisms may play an important role in the diabetic vascular complications and the accelerated atherosclerosis associated with diabetes and obesity. In addition, recent reports have shown that NAD(P)H oxidases exist in pancreatic β-cells and adipocytes, and this oxidase-generated ROS production may play an important role in both the progressive β-cell dysfunction and the dysregulated adipocytokine production and subsequent obesity-induced metabolic syndrome. These results suggest that an NAD(P)H oxidase activation may be a useful therapeutic target for preventing diabetic vascular complications, progressive β-cell dysfunction and metabolic syndrome.
Export Options
About this article
Cite this article as:
Inoguchi Toyoshi and Nawata Hajime, NAD(P)H Oxidase Activation: A Potential Target Mechanism for Diabetic Vascular Complications, Progressive β-Cell Dysfunction and Metabolic Syndrome, Current Drug Targets 2005; 6 (4) . https://dx.doi.org/10.2174/1389450054021927
DOI https://dx.doi.org/10.2174/1389450054021927 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
RNA Molecules in the Treatment of Human Diseases
Messenger and non-coding RNAs, including long and small transcripts, are mediators of gene expression. Gene expression at the RNA level shows significant aberrations in human diseases, including cancer, leukemia, lymphoma, cardiovascular diseases, and neurological disorders. Human transcripts serve either as biomarkers of diagnosis, prognosis, prediction of treatment response and/or therapy ...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
-
Lipid Disorders in Diabetes Mellitus and Current Management
Current Pharmaceutical Analysis Microglia NLRP3 Inflammasomes Activation Involving Diabetic Neuroinflammation in Diabetic Mice and BV2 Cells
Current Pharmaceutical Design Vascular Injury During Elevated Glucose can be Mitigated by Erythropoietin and Wnt Signaling
Current Neurovascular Research Telmisartan Inhibits Advanced Glycation End Products (AGEs)-Elicited Endothelial Cell Injury by Suppressing AGE Receptor (RAGE) Expression Via Peroxisome Proliferator-Activated Receptor-γ Activation
Protein & Peptide Letters Immunossupressant and Organ Transplantation: Immunophilins Targeting Agent and Alternative Therapies
Current Medicinal Chemistry Modulation of Angiotensin II Effects, A Potential Novel Approach to Inflammatory and Immune Diseases
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents The Injured Cochlea as a Target for Inflammatory Processes, Initiation of Cell Death Pathways and Application of Related Otoprotective Strategies
Recent Patents on CNS Drug Discovery (Discontinued) Stroke Subtypes and their Possible Implication in Stroke Prevention Drug Strategies
Current Vascular Pharmacology Suitable Antibacterial Substances for the Treatment of Urinary Tract Infections
Anti-Infective Agents in Medicinal Chemistry Detrimental Effects of Hyperglycemia in Acute Coronary Syndromes: from Pathophysiological Mechanisms to Therapeutic Strategies
Mini-Reviews in Medicinal Chemistry A New Protocol of Type 2 Diabetes Induction and Hydrocortisone Effects on Beta-Cells Signaling in Mice
Current Chemical Biology Mitochondrial genome sequencing in atherosclerosis: what's next?
Current Pharmaceutical Design Clinical Uses of 1-Alpha-Hydroxy-Ergocalciferol
Current Vascular Pharmacology Lipids and Non-Cardiac Vascular Disease: A Lecture Overview
Current Vascular Pharmacology Physiological Effect and Therapeutic Application of Alpha Lipoic Acid
Current Medicinal Chemistry Thrombomodulin – A New Target for Treating Stroke at the Crossroad of Coagulation and Inflammation
Current Medicinal Chemistry Diabetes, Diabetic Complications, and Phosphate Toxicity: A Scoping Review
Current Diabetes Reviews Role of CYP2E1 in Mitochondrial Dysfunction and Hepatic Injury by Alcohol and Non-Alcoholic Substances
Current Molecular Pharmacology Pharmacotherapy in Type 2 Diabetes: A Functional Schema for Drug Classification
Current Diabetes Reviews Effects of Mesenchymal Stromal Cells on Diabetic Cardiomyopathy
Current Pharmaceutical Design