Abstract
Aldose reductase [ALR2; EC 1.1.1.21], a key enzyme of polyol pathway, catalyzes NADPH-dependent reduction of glucose to sorbitol (Sorbitol pathway), and an excessive accumulation of intracellular sorbitol found in various tissues of diabetic animals and in cells cultured under high glucose conditions has been proposed to be an important factor for the pathogenesis of diabetic complications. The only strategy shown to be consistently beneficial in the treatment of diabetic complications is meticulous control of blood glucose. However, aldose reductase (AR) enzyme inhibition is becoming one of the therapeutic strategies that have been proposed to prevent or ameliorate long-term diabetic complications. Therefore, AR inhibitors (ARIs) hold promise for reducing metabolic nerve injury, but further study is needed. On the other hand, there is strong evidence to show that diabetes is associated with increased oxidative stress. However, the source of this oxidative stress remains unclear. This relationship between diabetic complications and free radical production was also under investigation. The studies suggest that hydroxyl radical is indirectly inhibited by ARIs resulting from decreasing polyol levels and hydroxyl radical formation is related to the early stages of diabetic complications, possibly via the Fenton reaction involving H2O2 produced from the activated polyol pathway. Therefore, it is proposed that hydroxyl radical may accelerate damage to the cell membranes resulting from polyol accumulation. The search for specific inhibitors of AR enzyme has still become a major pharmaceutic challenge, though a number of AR inhibitors have so far been assessed for diabetic complications.
Keywords: aldose reductase, diabetic complications, ar enzyme inhibitors
Current Medicinal Chemistry
Title: Recent Studies of Aldose Reductase Enzyme Inhibition for Diabetic Complications
Volume: 10 Issue: 15
Author(s): Sibel Suzen and Erdem Buyukbingol
Affiliation:
Keywords: aldose reductase, diabetic complications, ar enzyme inhibitors
Abstract: Aldose reductase [ALR2; EC 1.1.1.21], a key enzyme of polyol pathway, catalyzes NADPH-dependent reduction of glucose to sorbitol (Sorbitol pathway), and an excessive accumulation of intracellular sorbitol found in various tissues of diabetic animals and in cells cultured under high glucose conditions has been proposed to be an important factor for the pathogenesis of diabetic complications. The only strategy shown to be consistently beneficial in the treatment of diabetic complications is meticulous control of blood glucose. However, aldose reductase (AR) enzyme inhibition is becoming one of the therapeutic strategies that have been proposed to prevent or ameliorate long-term diabetic complications. Therefore, AR inhibitors (ARIs) hold promise for reducing metabolic nerve injury, but further study is needed. On the other hand, there is strong evidence to show that diabetes is associated with increased oxidative stress. However, the source of this oxidative stress remains unclear. This relationship between diabetic complications and free radical production was also under investigation. The studies suggest that hydroxyl radical is indirectly inhibited by ARIs resulting from decreasing polyol levels and hydroxyl radical formation is related to the early stages of diabetic complications, possibly via the Fenton reaction involving H2O2 produced from the activated polyol pathway. Therefore, it is proposed that hydroxyl radical may accelerate damage to the cell membranes resulting from polyol accumulation. The search for specific inhibitors of AR enzyme has still become a major pharmaceutic challenge, though a number of AR inhibitors have so far been assessed for diabetic complications.
Export Options
About this article
Cite this article as:
Suzen Sibel and Buyukbingol Erdem, Recent Studies of Aldose Reductase Enzyme Inhibition for Diabetic Complications, Current Medicinal Chemistry 2003; 10 (15) . https://dx.doi.org/10.2174/0929867033457377
DOI https://dx.doi.org/10.2174/0929867033457377 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
- Announcements
Related Articles
-
Patent Selections:
Recent Patents on Cardiovascular Drug Discovery Editorial (Hot Topic: Coming Back to Nature: Plants as a Vital Source of Pharmaceutically Important Metabolites – Part II A)
Current Medicinal Chemistry Silencing the Brain May be Better than Stimulating it. The GABA Effect
Current Pharmaceutical Design NMDA Neurotransmission Dysfunction in Mild Cognitive Impairment and Alzheimers Disease
Current Pharmaceutical Design Alzheimer's Disease: Related Targets, Synthesis of Available Drugs, Bioactive Compounds Under Development and Promising Results Obtained from Multi-target Approaches
Current Drug Targets Vascular Endothelial Growth Factor: A New Paradigm for Targeting Various Diseases
Current Angiogenesis (Discontinued) Future Therapeutic Directions: New Medications and Insulin Delivery in a Changing World for Effective Diabetes Management
Current Drug Discovery Technologies Molecular Insight into the Crosstalk of UPS Components and Alzheimer’s Disease
Current Protein & Peptide Science Protein Oxidative Modification in the Aging Organism and the Role of the Ubiquitin Proteasomal System
Current Pharmaceutical Design Neurogenic plasticity of mesenchymal stem cell, an alluring cellular replacement for traumatic brain injury
Current Stem Cell Research & Therapy Inhibition of Ataxia Telangiectasia-p53-E2F-1 Pathway in Neurons as a Target for the Prevention of Neuronal Apoptosis
Current Drug Metabolism Biomarkers and Future Targets for Development in Amyotrophic Lateral Sclerosis
Current Medicinal Chemistry Extrasynaptic GABA<sub>A</sub> Receptors in the Brainstem and Spinal Cord: Structure and Function
Current Pharmaceutical Design Therapeutical Potential of CB<sub>2</sub> Receptors in Immune-Related Diseases
Current Molecular Pharmacology Patent Selections:
Recent Patents on Food, Nutrition & Agriculture Neuroimmune Crosstalk in CNS Disorders: The Histamine Connection
Current Pharmaceutical Design Minocycline and Cytoprotection: Shedding New Light on a Shadowy Controversy
Current Drug Delivery Proteins in Microglial Activation - Inputs and Outputs by Subsets
Current Protein & Peptide Science Patient, System and Clinician Level Interventions to Address Disparities in Diabetes Care
Current Diabetes Reviews Emerging Potential of Citrus Flavanones as an Antioxidant in Diabetes and its Complications
Current Topics in Medicinal Chemistry