Chelation: A Fundamental Mechanism of Action of AGE Inhibitors, AGE Breakers, and Other Inhibitors of Diabetes Complications

• Published in: Diabetes (New York, N.Y.) Vol. 61; no. 3; pp. 549 - 559
• Main Authors: NAGAI, Ryoji, MURRAY, David B, METZ, Thomas O, BAYNES, John W
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.03.2012
• Subjects: 60 APPLIED LIFE SCIENCES; Advanced glycation end products; advanced glycation end-product (AGE); Age; AGE breaker; Aldehyde Reductase - antagonists & inhibitors; ANGIOTENSIN; Angiotensin Receptor Antagonists - therapeutic use; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Animals; Antihypertensive Agents - therapeutic use; BASIC BIOLOGICAL SCIENCES; Biological and medical sciences; CARBONYLS; Care and treatment; Chelating agents; Chelating Agents - therapeutic use; chelation; Diabetes; Diabetes Complications - drug therapy; Diabetes mellitus; Diabetes. Impaired glucose tolerance; DISEASES; Drinking water; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Environmental Molecular Sciences Laboratory; ENZYME INHIBITORS; Etiopathogenesis. Screening. Investigations. Target tissue resistance; FUNCTIONALS; Glucose; Glycation End Products, Advanced - antagonists & inhibitors; Glycation End Products, Advanced - physiology; Humans; HYDROLYSIS; Hyperglycemia; Hypotheses; INFLAMMATION; Kinases; Medical sciences; Metabolism; metal-catalyzed oxidation; MODIFICATIONS; OXIDATION; Oxidative stress; Pathogenesis; Physiological aspects; PROTEINS; REACTION INTERMEDIATES; s in Diabetes; THERAPY; TRAPPING; Vitamin B; Endocrinopathy; Complication; Mechanism of action; Diabetes mellitus; Age
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db11-1120

This article outlines evidence that advanced glycation end product (AGE) inhibitors and breakers act primarily as chelators, inhibiting metal-catalyzed oxidation reactions that catalyze AGE formation. We then present evidence that chelation is the most likely mechanism by which ACE inhibitors, angiotensin receptor blockers, and aldose reductase inhibitors inhibit AGE formation in diabetes. Finally, we note several recent studies demonstrating therapeutic benefits of chelators for diabetic cardiovascular and renal disease. We conclude that chronic, low-dose chelation therapy deserves serious consideration as a clinical tool for prevention and treatment of diabetes complications.