Abstract
Diabetic patients have a two- to four-fold increased risk for the development of microvascular (renal, neuronal and retinal) and macrovascular complications. Unfortunately, these complications may develop in both Type 1 and Type 2 diabetic patients even with careful glycaemic, blood pressure and lipid control. With the worldwide increase in the incidence diabetes, new strategies to prevent the complications are urgently needed. Mediators of vascular damage of diabetes include poor glycemic control, lipoprotein abnormalities, hypertension, oxidative stress, inflammation and advanced glycation end-products (AGEs), which are modified proteins formed by non-enzymatic glycation. AGEs are resistant to enzymatic degradation and therefore very stable, thus their accumulation continues throughout aging. AGE accumulation causes arterial stiffening in the vessel wall, glomerulosclerosis in the kidney, and vascular hyperpermeability in the retina. Through their interaction with their putative receptor the so-called receptor for AGEs (RAGE), AGEs activate endothelial cells and macrophages, generate reactive oxygen species (ROS), induce overexpression of vascular endothelial growth factor (VEGF) and vascular cell adhesion molecule-1 (VCAM-1), and quench nitric oxide (NO). The pharmacological treatment currently available for either Type 1 or Type 2 diabetic patients does not directly address the excess accumulation of AGEs. Novel compounds that inhibit AGE formation, cleave AGE crosslinks or reverse their interaction with RAGE are now accessible and could prove useful in meeting this challenge. Other strategies such as inhibition of the hexosamine pathway, vitamin therapy to reduce oxidation and AGE accumulation, reduction of the ROS, or blocking the actions of growth factors or intracellular messengers of cell differentiation are also currently under research. This review will recount recent advances in the development of therapeutic approaches for inhibiting and treating the development of diabetic end-organ damage.
Keywords: Diabetes, Nephropathy, Retinopathy, Neuropathy, Cardiovascular disease, Glycation, Oxidation, Advanced, glycation end-product
Current Medicinal Chemistry
Title: Novel Therapeutics for Diabetic Micro- and Macrovascular Complications
Volume: 13 Issue: 15
Author(s): A. Soro-Paavonen and J. M. Forbes
Affiliation:
Keywords: Diabetes, Nephropathy, Retinopathy, Neuropathy, Cardiovascular disease, Glycation, Oxidation, Advanced, glycation end-product
Abstract: Diabetic patients have a two- to four-fold increased risk for the development of microvascular (renal, neuronal and retinal) and macrovascular complications. Unfortunately, these complications may develop in both Type 1 and Type 2 diabetic patients even with careful glycaemic, blood pressure and lipid control. With the worldwide increase in the incidence diabetes, new strategies to prevent the complications are urgently needed. Mediators of vascular damage of diabetes include poor glycemic control, lipoprotein abnormalities, hypertension, oxidative stress, inflammation and advanced glycation end-products (AGEs), which are modified proteins formed by non-enzymatic glycation. AGEs are resistant to enzymatic degradation and therefore very stable, thus their accumulation continues throughout aging. AGE accumulation causes arterial stiffening in the vessel wall, glomerulosclerosis in the kidney, and vascular hyperpermeability in the retina. Through their interaction with their putative receptor the so-called receptor for AGEs (RAGE), AGEs activate endothelial cells and macrophages, generate reactive oxygen species (ROS), induce overexpression of vascular endothelial growth factor (VEGF) and vascular cell adhesion molecule-1 (VCAM-1), and quench nitric oxide (NO). The pharmacological treatment currently available for either Type 1 or Type 2 diabetic patients does not directly address the excess accumulation of AGEs. Novel compounds that inhibit AGE formation, cleave AGE crosslinks or reverse their interaction with RAGE are now accessible and could prove useful in meeting this challenge. Other strategies such as inhibition of the hexosamine pathway, vitamin therapy to reduce oxidation and AGE accumulation, reduction of the ROS, or blocking the actions of growth factors or intracellular messengers of cell differentiation are also currently under research. This review will recount recent advances in the development of therapeutic approaches for inhibiting and treating the development of diabetic end-organ damage.
Export Options
About this article
Cite this article as:
Soro-Paavonen A. and Forbes M. J., Novel Therapeutics for Diabetic Micro- and Macrovascular Complications, Current Medicinal Chemistry 2006; 13 (15) . https://dx.doi.org/10.2174/092986706777452515
DOI https://dx.doi.org/10.2174/092986706777452515 |
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
Approaches to the Treatment of Chronic Inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...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

- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
Editorial (Thematic Issue: New Therapeutic Targets in Clinical Medicine)
Current Pharmaceutical Design Genetic Predisposition in NAFLD and NASH: Impact on Severity of Liver Disease and Response to Treatment
Current Pharmaceutical Design Molecular Docking Study of Catecholamines and [4-(Propan-2-yl) Phenyl]Carbamic acid with Tyrosine Hydroxylase
CNS & Neurological Disorders - Drug Targets Editorial [Hot Topic: Metabolic Syndrome in an Asian Chinese Population and Agents and Targets for Cardiovascular Protection (Guest Editors: M.L. Fung and T.M. Wong)]
Cardiovascular & Hematological Disorders-Drug Targets Important Aspects of Post-Prandial Antidiabetic Drug, Acarbose
Current Topics in Medicinal Chemistry Current Status of Rho-Associated Kinases (ROCKs) in Coronary Atherosclerosis and Vasospasm
Cardiovascular & Hematological Agents in Medicinal Chemistry The Role of Angiotensin in Obesity and Metabolic Disease
Endocrine, Metabolic & Immune Disorders - Drug Targets Prevention of Ischemic Stroke: Antithrombotic Therapy in Cardiac Embolism
Current Drug Targets Comparative Effect of Telmisartan vs Lisinopril on Blood Pressure in Patients of Metabolic Syndrome
Endocrine, Metabolic & Immune Disorders - Drug Targets Is BMI Associated with COVID-19 Severity? A Retrospective Observational Study
Current Medicinal Chemistry Multiple Sclerosis and Neuroinflammation: The Overview of Current and Prospective Therapies
Current Pharmaceutical Design Clinical Perspectives on the Role of Anti-Platelet and Statin Therapy in Patients with Vascular Diseases
Current Vascular Pharmacology Cell Penetrating Peptide-Mediated Caveolae-Dependent Activation of Lung Endothelial Nitric Oxide Synthase
Protein & Peptide Letters Angiotensin Converting Enzyme 2 Activator (DIZE) Modulates Metabolic Profiles in Mice, Decreasing Lipogenesis
Protein & Peptide Letters Variation of Antioxidant Capacity in Different Layers of Onion (Allium cepa L.) At Two Different Stages of Maturation
Current Nutrition & Food Science Brain MRI, Apoliprotein E Genotype, and Plasma Homocysteine in American Indian Alzheimer Disease Patients and Indian Controls
Current Alzheimer Research Hydrogen Sulfide: Physiological Roles and Therapeutic Implications against COVID-19
Current Medicinal Chemistry Types of Voltage-Gated Calcium Channels: Molecular and Electrophysiological Views
Current Hypertension Reviews Patent Selections:
Recent Patents on CNS Drug Discovery (Discontinued) MicroRNAs and the Heart: Small Things Do Matter
Current Topics in Medicinal Chemistry