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

• Published in: Journal of the neurological sciences 2012-04, Vol.315 (1), p.60-63
• Main Authors: Bursova, Sarka, Dubovy, Petr, Vlckova-Moravcova, Eva, Nemec, Martin, Klusakova, Ilona, Belobradkova, Jana, Bednarik, Josef
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - physiopathology; Diabetic Neuropathies - genetics; Diabetic Neuropathies - metabolism; Diabetic Neuropathies - physiopathology; Diabetic neuropathy; Female; GAP-43 Protein - biosynthesis; GAP-43 Protein - genetics; Gene Expression Regulation; Growth-associated protein 43; Humans; Injuries of the nervous system and the skull. Diseases due to physical agents; Male; Medical sciences; Middle Aged; Nerve Fibers - physiology; Nerve Fibers, Unmyelinated - pathology; Nerve Fibers, Unmyelinated - physiology; Nerve Regeneration - genetics; Neurology; Pilot Projects; Protein gene product 9.5; Regeneration; Skin - innervation; Skin - metabolism; Skin biopsy; Traumas. Diseases due to physical agents; Type 2 diabetes mellitus
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2011.11.038

Abstract 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.