Naslov
Advanced glycation endproducts in peripheral nerve in type 2 diabetes with neuropathy

Autori
Mišur, Irena ; Žarković, Kamelija ; Barada, Ante ; Batelja, Lovorka ; Miličević, Zvonko ; Turk, Zdenka

Izvornik
Acta Diabetologica (0940-5429) 41 (2004), 4; 158-166

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Diabetic polyneuropathy; Advanced glycation endproduct (AGE); Peripheral nerve; Immunohistochemistry.

Sažetak
Advanced glycation endproducts accumulate over proteins as a consequence of diabetic hyperglycaemia, and thus contribute to the pathogenesis of diabetic complications. To improve the understanding of the pathology of diabetic neuropathy, AGE accumulation was analysed in sural and/or femoral nerves obtained under spinal anaesthesia from type 2 diabetic patients (n=8) with both distal symmetrical polyneuropathy and proximal neuropathy. Pronounced AGE immunoreactivity was detected on axons and myelin sheaths in 90% of diabetic peripheral nerves but not in the control specimen. The intensity of axonal AGE immunopositivity significantly correlated with the severity of morphological alterations (p<0.005). AGE localisation, demonstrated by immunohistochemical methods, was also present in the endoneurium, perineurium and microvessels. Morphometric analysis of the diabetic peripheral nerve showed perineurial thickening (DM vs C: 15.5&#61617; 4.9 vs 6.6&#61617; 2.1 &#61549; m, p<0.001), narrowing of the microvessel lumina (DM vs C: 66.6&#61617; 50.5 vs 579.5&#61617; 38.4 x103 &#61549; m2, p<0.000) and significant reduction in the number of preserved axons (DM vs C: 3.6&#61617; 3 vs 8.9&#61617; 2.3 per area of 105 &#61549; m2, p<0.037). In the present study, the sera of diabetic patients were shown to contain autoantibodies to epitope(s) of AGE structure. Additionally, the presence of soluble immune complexes containing AGE moiety was demonstrated. In conclusion, these results provide evidence for excessive AGE formation on peripheral nerve components, primarily on axons, and a significantly higher level of circulating AGE-immune complexes in patients with both distal diabetic polyneuropathy and proximal neuropathy.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA