Advanced Glycation End Products in Extracellular Matrix Proteins Contribute to the Failure of Sensory Nerve Regeneration in Diabetes

• DOI: 10.2337/db09-0320
• Publication Date: 2009-09-01T01:06:51Z
• Authors: Beatriz Duran-Jim...; Darin Dobler; Sarah Moffatt; Naila Rabbani; Charles H. Streuli; Paul J. Thornalley; David R. Tomlinson; Natalie J. Gardiner
• Keywords: Neurite; Endoneurium

OBJECTIVE The goal of this study was to characterize glycation adducts formed in both vivo extracellular matrix (ECM) proteins endoneurium from streptozotocin (STZ)-induced diabetic rats and vitro by laminin fibronectin with methylglyoxal glucose. We also investigated the impact advanced end product (AGE) residue content ECM on neurite outgrowth sensory neurons. RESEARCH DESIGN AND METHODS Glycation, oxidation, nitration extracted control STZ-induced rat sciatic nerve (3–24 weeks post-STZ) that had been glycated using glucose or were examined liquid chromatography tandem mass spectrometry. Methylglyoxal-glycated unmodified used as substrata for dissociated neurons models regeneration. RESULTS diabetes produced a significant increase early Nε-fructosyl-lysine AGE contents endoneurial ECM. Glycation increased adduct methylglyoxal-derived hydroimidazolone Nε-fructosyl-lysine, respectively, greatest quantitative importance. caused decrease neurotrophin-stimulated preconditioned outgrowth. This prevented aminoguanidine. decreased outgrowth, which aminoguanidine growth factor. CONCLUSIONS Early markedly diabetes. causes reduction may provide mechanism failure collateral sprouting axonal regeneration neuropathy.