A New Perspective on Therapeutic Inhibition of Advanced Glycation in Diabetic Microvascular Complications: Common Downstream Endpoints Achieved Through Disparate Therapeutic Approaches?

Vol. 30, No. 4, 2009

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Kidney and beyond - Review Article

A New Perspective on Therapeutic Inhibition of Advanced Glycation in Diabetic Microvascular Complications: Common Downstream Endpoints Achieved Through Disparate Therapeutic Approaches?
Karly C. Sourris^a, Brooke E. Harcourt^{a, b}, Josephine M. Forbes^{a, b}

^aJDRF Einstein Centre for Diabetes Complications, Diabetes and Metabolism Division, Baker IDI Heart and Diabetes Institute, and
^bDepartment of Immunology, Monash University, AMREP Precinct, Melbourne, Vic., Australia

Address of Corresponding Author

Am J Nephrol 2009;30:323-335 (DOI: 10.1159/000226586)

Key Words

Advanced glycation end products
Diabetic nephropathy
Reactive oxygen species
Receptor for advanced glycation end products

Abstract

A commonality among the chemically disparate compounds that inhibit the formation and accumulation of advanced glycation end products (AGEs) or their signalling pathways is their end organ protection in experimental models of diabetes complications. Although this group of therapeutics are structurally and functionally distinct with numerous mechanisms of action, the most important factor governing their therapeutic capability is clearly their ability to alleviate the tissue burden of advanced glycation, rather than the biochemical mechanism by which this is achieved. However, it remains to be determined if it is the reduction in tissue AGE levels per se or inhibition of downstream signal pathways which is ultimately required for end organ protection. For example, a number of these agents stimulate antioxidant defences, modify lipid profiles and inhibit low-grade inflammation. These novel actions emphasise the importance of further examination of the advanced glycation pathway and in particular the diverse action of these agents in ameliorating the development of diabetic complications such as nephropathy.

Author Contacts

Karly C. Sourris
JDRF Einstein Centre for Diabetes Complications
Baker IDI Heart and Diabetes Institute, PO Box 6492
St Kilda Road Central, Melbourne, Vic. 8008 (Australia)
Tel. +61 3 8532 1124, Fax +61 3 8532 1288, E-Mail Karly.Sourris@bakeridi.edu.au

Article Information

Received: April 15, 2009
Accepted: May 25, 2009
Published online: June 29, 2009
Number of Print Pages : 13
Number of Figures : 0, Number of Tables : 1, Number of References : 182

Medline Abstract (ID 19556753)

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