A new perspective on therapeutic inhibition of advanced glycation in diabetic microvascular complications: common downstream endpoints achieved through disparate therapeutic approaches?
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.
Sourris
Karly C
KC
JDRF Einstein Centre for Diabetes Complications, Diabetes and Metabolism Division, Baker IDI Heart and Diabetes Institute, PO Box 6492 St Kilda Road Central, Melbourne, Vic. 8008, Australia. Karly.Sourris@bakeridi.edu.au
Harcourt
Brooke E
BE
Forbes
Josephine M
JM
D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008833:Microcirculation; D017382:Reactive Oxygen Species / Q000378:metabolism; D013722:Teprotide / Q000627:therapeutic use; D014815:Vitamins / Q000627:therapeutic use
D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; D017382:Reactive Oxygen Species; D014815:Vitamins; D013722:Teprotide