Expression of growth-associated protein 43 in the skin nerve fibers of patients with type 2 diabetes mellitus

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Authors

DIVIŠOVÁ Šárka DUBOVÝ Petr VLČKOVÁ Eva NĚMEC Martin KLUSÁKOVÁ Ilona BĚLOBRÁDKOVÁ Jana BEDNAŘÍK Josef

Year of publication 2012
Type Article in Periodical
Magazine / Source Journal of Neurological Sciences
MU Faculty or unit

Central European Institute of Technology

Citation
Web http://www.ncbi.nlm.nih.gov/pubmed/22209024
Doi http://dx.doi.org/10.1016/j.jns.2011.11.038
Field Neurology, neurosurgery, neurosciences
Keywords Growth-associated protein 43; protein gene product 9.5; skin biopsy; type 2 diabetes mellitus; diabetic neuropathy; regeneration
Description The growth-associated protein 43 (GAP-43) is known as a marker of regenerating nerve fibers and their continuous remodeling in the adult human skin. The purpose of this pilot study was to investigate a possible role for GAP-43 in the detection of the early stages of small-fiber neuropathy in patients with type 2 diabetes mellitus (DM2) as compared with a well- established and validated parameter – intra-epidermal nerve fiber density (IENFD) of protein gene product 9.5 (PGP 9.5) immunoreactive intra-epidermal C fibers. In a group of 21 patients with DM2 within three years of diagnosis (13 men, 8 women; mean age 53.9 +- 12.8; range 30 – 74) and a group of 17 healthy volunteers (8 men, 9 women; mean age 55.8 +- 8.5; range 45 – 70 years), skin punch biopsies were taken from a distal calf and double immunostained with both PGP 9.5 and GAP-43. In healthy controls, 96.8% of 629 PGP 9.5 immunoreactive fibers were immunostained with GAP-43; the proportion of PGP 9.5 intra-epidermal nerve fibers immunoreactive for GAP-43 in control subjects ranged from 86.5 to 100%. In DM2 patients, IENFD was significantly lower compared to controls (median, 1.5 vs. 11.2/mm; p <0.001). The proportion of GAP-43 immunoreactive intraepidermal nerve fibers was significantly lower in DM2 patients compared to healthy controls (73.6% of 337 PGP 9.5 positive fibers; p <0.001); ranged from 0 to 98.1%. In conclusion, these results show that impaired regeneration of intra-epidermal C fibers in the early stages of type 2 diabetes mellitus, as indicated by GAP-43, might be a marker of incipient diabetic neuropathy.
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