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J Diabetes Res. 2018 Dec 10;2018:2309108. doi: 10.1155/2018/2309108. eCollection 2018.

Preserved Expression of Skin Neurotrophic Factors in Advanced Diabetic Neuropathy Does Not Lead to Neural Regeneration despite Pancreas and Kidney Transplantation.

Author information

1
Diabetes Center, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic.
2
Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic.
3
Clinical and Transplant Pathology Department, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic.
4
Department of Statistics, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic.
5
University Hospital of Würzburg, Department of Neurology, 97080 Würzburg, Germany.

Abstract

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes with potential severe consequences. Its pathogenesis involves hyperglycemia-linked mechanisms, which may include changes in the expression of neurotrophic growth factors. We analyzed the expression of 29 factors potentially related to nerve degeneration and regeneration in skin biopsies from 13 type 1 diabetic pancreas and kidney recipients with severe DPN including severe depletion of intraepidermal nerve fibers (IENF) in lower limb skin biopsies (group Tx1 1st examination). The investigation was repeated after a median 28-month period of normoglycemia achieved by pancreas transplantation (group Tx1 2nd examination). The same tests were performed in 13 stable normoglycemic pancreas and kidney recipients 6-12 years posttransplantation (group Tx2), in 12 matched healthy controls (group HC), and in 12 type 1 diabetic subjects without severe DPN (group DM). Compared to DM and HC groups, we found a significantly higher (p < 0.05-0.001) expression of NGF (nerve growth factor), NGFR (NGF receptor), NTRK1 (neurotrophic receptor tyrosine kinase 1), GDNF (glial cell-derived neurotrophic factor), GFRA1 (GDNF family receptor alpha 1), and GFAP (glial fibrillary acidic protein) in both transplant groups (Tx1 and Tx2). Enhanced expression of these factors was not normalized following the median 28-month period of normoglycemia (Tx1 2nd examination) and negatively correlated with IENF density and with electrophysiological indices of DPN (vibration perception threshold, electromyography, and autonomic tests). In contrast to our expectation, the expression of most of 29 selected factors related to neural regeneration was comparable in subjects with severe peripheral nerve fiber depletion and healthy controls and the expression of six factors was significantly upregulated. These findings may be important for better understanding the pathophysiology of nerve regeneration and for the development of intervention strategies.

PMID:
30648113
PMCID:
PMC6311823
DOI:
10.1155/2018/2309108
[Indexed for MEDLINE]
Free PMC Article

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