Advanced glycation end products

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Abstract

Prolonged hyperglycemia, dyslipidemia and oxidative stress in diabetes result in the increased production and accumulation of advanced glycation end products (AGEs) in the kidney. Covalent AGE modifications significantly influence the structure and function of key protein targets. In addition, activation of AGE receptors, alone or in combination with other ligands, is able to promote renal damage, fibrosis and inflammation associated with diabetic nephropathy. The actions of AGEs synergize and potentiate the activity of other pathogenic mediators in the diabetic kidney, including oxidative stress, protein kinase C and renin-angiotensin system activation, which subsequently promote the development and progression of kidney disease in a vicious and progressive cycle. Their importance as downstream mediators of hyperglycemia in diabetes has been amply demonstrated in studies using mechanistically different inhibitors of advanced glycation to retard the development of kidney disease without directly influencing plasma glucose levels. Furthermore, direct exposure to AGEs is able to generate lesions similar to those seen in diabetic nephropathy. The human body has a number of natural defenses against AGE accumulation, which are reduced in diabetic individuals, and in particular those with nephropathy, while the receptor for AGEs and its ligands are significantly increased. Given such data, a number of different pharmacological agents have been developed to reduce AGEs and with it prevent diabetic kidney disease. Although many have proved effective in experimental models of diabetes, their clinical utility remains unproven.

Original languageEnglish
Title of host publicationDiabetes and The Kidney
EditorsKar Neng Lai, Sydney Tang
PublisherS Karger AG
Pages66-74
Number of pages9
ISBN (Electronic)9783805597432
ISBN (Print)9783805597425
DOIs
Publication statusPublished - 1 Jun 2011
Externally publishedYes

Publication series

NameContributions to Nephrology
Volume170
ISSN (Print)0302-5144

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