Advanced glycation end products inhibitor
(2011) Studies on Renal Disorders Studies on Renal Disorders — ISBN: [978-1-60761-856-0], p. 389-406, published
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- Early intensive glycemic control in both type 1 and type 2 diabetes mellitus retards in the long term the development and progression of microvascular complications such as diabetic nephropathy, even despite a worsening glycemic control. This phenomenon is a so-called metabolic memory or legacy effect, partly ascribed to the advanced glycation end products (AGEs), whose formation is closely linked to the glycoxidative biology. In this chapter we summarize the role of AGEs and their receptor (receptor for AGEs: RAGE) in the onset and progression of diabetic vascular complications, especially in diabetic nephropathy, and review current and future treatment strategies targeting the AGE-RAGE system, including (a) AGE formation inhibitor (including angiotensin receptor blocker [ARB]), (b) AGE cross-link breaker, (c) RAGE antagonist, (d) AGE binder including sRAGE (soluble receptor for AGEs), and (e) hypoxia-inducible factor (HIF) activator. Several inhibitors of tissue accumulation of AGEs in diabetes have been clinically tested, including inhibitors of AGE formation, such as aminoguanidine, benfotiamine, and pyridoxamine, or AGE cross-link breakers, such as ALT-711. The clinical benefits of ARBs to protect the kidney are, at least in part, due to the inhibition of AGE formation. Recently antagonists of the peroxisome proliferator-activated receptor-g (PPAR-g), such as rosiglitazone and pioglitazone, which also provide renal benefits clinically, have been recognized as RAGE antagonists. Oral adsorbents, such as AST-120 (Kremezin) and Sevelamer carbonate, bind AGEs and reduce their plasma levels in experimental models. Several other approaches relying on the AGE hypothesis have been proposed to treat diabetic complications in experimental models, but their benefits are yet to be documented clinically. In summary, inhibition of the AGE-RAGE system confers some degree of experimental or clinical protection against diabetic microvascular complications, albeit to different degrees and by different mechanisms
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Dan, T., Van Ypersele de Strihou, C., & Miyata, T. (2011). Advanced glycation end products inhibitor. In Miyata, Toshio (ed.), Studies on Renal Disorders Studies on Renal Disorders (p. p. 389-406). Springer Science+Business Media. https://hdl.handle.net/2078.5/159321