Role of the AGE crosslink breaker, alagebrium, as a renoprotective agent in diabetes.
The biochemical process of advanced glycation appears to play a central role in the development and progression of diabetic vascular complications. A number of strategies to influence this pathway have been designed, one of which involves the putative advanced glycation end-product (AGE) crosslink breaker, alagebrium which has been shown in in vitro studies to cleave preformed AGE crosslinks. This agent has been studied in various models of diabetic complications and has been shown to attenuate diabetic renal disease, cardiac dysfunction, and atherosclerosis. In addition to the ability of alagebrium to reduce tissue levels of AGEs, this drug appears to inhibit activation of certain protein kinase C isoforms. Planned clinical studies in diabetic subjects at risk of complications should assist in determining the role of alagebrium in the prevention, retardation, and reversal of diabetic micro- and macrovascular disease.
Coughlan
M T
MT
JDRF Einstein Centre for Diabetic Complications, Diabetes and Metabolism Division, Baker Heart Research Institute, Melbourne, Victoria, Australia.
Forbes
J M
JM
Cooper
M E
ME
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology; D013844:Thiazoles / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D007527:Isoenzymes; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D013844:Thiazoles; C406794:alagebrium; D011493:Protein Kinase C