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Neurotrophin-3 is increased in skin in human diabetic neuropathy
  1. A J Kennedya,
  2. A Wellmera,
  3. P Facera,
  4. G Saldanhaa,
  5. P Kopelmanb,
  6. R M Lindsayc,
  7. P Ananda
  1. aAcademic Department of Neurology, bDiabetes and Metabolism, St Bartholomew’s and the Royal London School of Medicine and Dentistry, UK, cRegeneron Pharmaceuticals Inc, Tarrytown, New York, USA
  1. Dr Praveen Anand, Academic Department of Neurology, St Bartholomew’s and the Royal London School of Medicine and Dentistry, The Royal London Hospital, Whitechapel, London E1 1BB, UK. Telephone and fax 0044 171 377 7286; emailp.anand{at}


Neurotrophin-3 (NT-3), a member of the neurotrophin family, has been shown to be necessary for the development of muscle spindle and Merkel cell afferent nerve fibres in animal models.The presence of NT-3 in the suprabasal epidermis, where many unmyelinated sensory fibres terminate, has been shown for the first time. As these fibres are affected in early diabetic neuropathy and a clinical trial of recombinant human NT-3 in diabetic neuropathy is in progress, the concentrations of endogenous NT-3 in skin of 24 patients at different stages of diabetic polyneuropathy have been investigated. NT-3 concentrations, measured with a specific immunoassay, were significantly higher in affected skin biopsies from patients with diabetic neuropathy than matched control skin (diabetic skin 6.32 (1.18) pg/mg v control skin 1.28 (0.05) (mean (SEM)); p<0.004, Mann-Whitney Utest), particularly in the later stages. The optical density of NT-3-immunostaining was also significantly greater in the epidermis in diabetic patients (diabetic epidermis 0.30 (0.06)v controls 0.24 (0.01); p<0.02). No correlation was found between individual quantitative sensory tests and the increase of NT-3 concentration. The increase of NT-3 seems to reflect the degree of skin denervation in diabetic neuropathy, and may represent a compensatory mechanism. The concentrations of NT-3 in other peripheral targets deserve study in diabetic neuropathy.

  • diabetic neuropathy
  • neurotrophin-3
  • human skin
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