Exp Clin Endocrinol Diabetes 2005; 113(5): 288-291
DOI: 10.1055/s-2005-865600
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

The AGE/RAGE/NF-κB Pathway May Contribute to the Pathogenesis of Polyneuropathy in Impaired Glucose Tolerance (IGT)

K.-M. Haslbeck1 , E. Schleicher2 , A. Bierhaus3 , P. Nawroth3 , M. Haslbeck4 , B. Neundörfer1 , D. Heuss1
  • 1Department of Neurology, University of Erlangen-Nürnberg, Germany
  • 2Department of Medicine IV, University of Tübingen, Germany
  • 3Department of Medicine I, University of Heidelberg, Germany
  • 4Diabetes Research Institute, München, Germany
Weitere Informationen

Publikationsverlauf

Received: November 11, 2004 First decision: January 5, 2005

Accepted: March 17, 2005

Publikationsdatum:
30. Mai 2005 (online)

Abstract

Binding of ligands to the receptor for advanced glycation end products (RAGE) results in activation of the transcription factor nuclear factor kappa B (NF-κB) and subsequent expression of NF-κB-regulated cytokines. This has been shown to be a relevant pathomechanism in diabetic polyneuropathies (PNP). To determine whether this pathway may contribute to the pathogenesis of PNP due to impaired glucose tolerance (IGT) we performed a pilot study to demonstrate the presence of the RAGE ligand Nε-(Carboxymethyl)lysine (CML), the receptor itself and NF-κB in sural nerve biopsies of 4 patients with IGT-related PNP. Biopsies of either 4 patients with diabetic PNP and with Charcot-Marie-Tooth disease (CMT) I and II served as positive and negative controls, respectively. In IGT-related PNP and diabetic PNP, CML, RAGE, and NF-κB was found in the perineurium, epineurial vessels and in part in endoneurial vessels. CMT patients showed, if any, only weak staining for one or the other antigen. These data suggest that activation of the RAGE pathway may be one of the first steps in the pathogenesis of PNP even before chronic hyperglycemia occurs.

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Dr. med. Karl Matthias Haslbeck

Neurologische Klinik mit Poliklinik der Universität Erlangen-Nürnberg

Schwabachanlage 6

91054 Erlangen

Germany

Telefon: + 4991318534340

Fax: + 49 91 318 53 44 36

eMail: matthias.haslbeck@neuro.imed.uni-erlangen.de