engleski

Advanced glycation endproducts in human diabetic peripheral nerve

Nonenzymatic glycation leading to AGE formation is one of the important biochemical pathway involved in the development of the long-term diabetic complications and with a potential role in diabetic neuropathy. The aim of our study was in situ detection of AGE-immunoreactivity in sural and femoral nerve from type 2 diabetic patients with proximal diabetic neuropathy (PDN). Twelve patients with classic, abrupt-onset, sensorimotor form of PDN were included in the study (age 65.0 6.6 yrs, m/f 7/5, diabetes duration 12.5 5.6 yrs, PDN duration 4.2 1.7 mo, HbA1c 7.7%). The specimens were collected by biopsy of a small sensory branch of the femoral and sural nerve and AGE deposits were detected by an indirect immunofluorescence technique. The primary antibody was polyclonal anti-AGE. Competitive ELISA was measured total serum AGEs and blocking ELISA was used for the measurement of anti-AGE autoantibodies. Soluble AGE-immune complexes were detected by immunochemical method. Immunohistochemical examination under fluorescence microscope demonstrated AGE deposit located in the perineurium, focally in the endoneurium, and in the myelin protein area of diabetic nerves. A strong AGE positivity was detected in five out of six femoral nerve samples, and was located mainly in the myelin sheath. In sural nerve sections AGE deposition was found in the myelin, perineurium, and focally in the endoneurium. Six of them showed positivity in all the patterns, while in one sural nerve section AGE deposit appeared in the perineurium only. The AGE-immunoreactivity in control speciment was negative or very low intensity. Total AGEs, free anti-AGE antibodies and circulating AGE-IC were significantly higher in diabetic (n=12) than in control (n=20) serum samples (AGEs: 38.6 6.9 vs 25.1 7.2 ugEq/ml, p<0.00 ; Anti-AGE antibodies 58.7 20.2 vs 17.4 15.4 AU, p<0.00 ; AGE-IC 5.9 2.4 vs 3.39 1.1 AU ; p<0.00) Our study demonstrate excessive AGE deposition on periferal nerve cytoskeletal and myelin protein components, and significantly higher circulating AGE-immune complexes in condition of human diabetic neuropathy.

diabetes; glycation; peripheral nerve

DOI: 10.1007/BF03180172