title: Accumulation of fructosyl-lysine and advanced glycation end products in the kidney, retina and peripheral nerve of streptozotocin-induced diabetic rats.
abstract: The accumulation of AGEs (advanced glycation end products) in diabetes mellitus has been implicated in the biochemical dysfunction associated with the chronic development of microvascular complications of diabetes--nephropathy, retinopathy and peripheral neuropathy. We investigated the concentrations of fructosyl-lysine and AGE residues in protein extracts of renal glomeruli, retina, peripheral nerve and plasma protein of streptozotocin-induced diabetic rats and normal healthy controls. Glycation adducts were determined by LC with tandem MS detection. In diabetic rats, the fructosyl-lysine concentration was increased markedly in glomeruli, retina, sciatic nerve and plasma protein. The concentrations of N (epsilon)-carboxymethyl-lysine and N (epsilon)-carboxyethyl-lysine were increased in glomeruli, sciatic nerve and plasma protein, and N(epsilon)-carboxymethyl-lysine also in the retina. Hydroimidazolone AGEs derived from glyoxal, methylglyoxal and 3-deoxylglucosone were major AGEs quantitatively. They were increased in the retina, nerve, glomeruli and plasma protein. AGE accumulation in renal glomeruli, retina, peripheral nerve and plasma proteins is consistent with a role for AGEs in the development of nephropathy, retinopathy and peripheral neuropathy in diabetes. High-dose therapy with thiamine and Benfotiamine suppressed the accumulation of AGEs, and is a novel approach to preventing the development of diabetic complications.
authors.affiliation: Department of Biological Sciences, University of Essex, Central Campus, Wivenhoe Park, Colchester, Essex CO4 3SQ, U.K.
authors.forename: N
authors.initials: N
authors.lastname: Karachalias
authors.forename: R
authors.initials: R
authors.lastname: Babaei-Jadidi
authors.forename: N
authors.initials: N
authors.lastname: Ahmed
authors.forename: P J
authors.initials: PJ
authors.lastname: Thornalley
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism*; D013058:Mass Spectrometry; D010525:Peripheral Nerves / Q000378:metabolism*; D051381:Rats; D012160:Retina / Q000378:metabolism*; D013311:Streptozocin
chemical_list: C033186:fructosyl-lysine; D013311:Streptozocin; D008239:Lysine