Expression of growth-associated protein 43 in the skin nerve fibers of patients with type 2 diabetes mellitus.
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.
Department of Neurology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic. bursova@email.cz
Sarka
S
Bursova
Petr
P
Dubovy
Eva
E
Vlckova-Moravcova
Martin
M
Nemec
Ilona
I
Klusakova
Jana
J
Belobradkova
Josef
J
Bednarik
D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D019922:GAP-43 Protein / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000502:physiology; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology / Q000502:physiology*; D009416:Nerve Regeneration / Q000235:genetics; D010865:Pilot Projects; D012867:Skin / Q000294:innervation / Q000378:metabolism*
D019922:GAP-43 Protein