title: Advanced glycation end products.
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.
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Vic., Australia.
authors.forename: Merlin C
authors.initials: MC
authors.lastname: Thomas
mesh_terms: D000818:Animals; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000502:physiology*; D006031:Glycosylation; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced