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Proinsulin C-peptide replacement in type 1 diabetic BB/Wor-rats prevents deficits in nerve fiber regeneration.
J Neuropathol Exp Neurol. 2003 Jul; 62(7):765-79.JN

Abstract

We recently reported that early gene responses and expression of cytoskeletal proteins are perturbed in regenerating nerve in type 1 insulinopenic diabetes but not in type 2 hyperinsulinemic diabetes. We hypothesized that these differences were due to impaired insulin action in the former type of diabetes. To test this hypothesis, type 1 diabetic BB/Wor-rats were replaced with proinsulin C-peptide, which enhances insulin signaling without lowering blood glucose. Following sciatic nerve crush injury, early gene responses such as insulin-like growth factor, c-fos, and nerve growth factor were examined longitudinally in sciatic nerve. Neurotrophic factors, their receptors, and beta-tubulin and neurofilament expression were examined in dorsal root ganglia. C-peptide replacement significantly normalized early gene responses in injured sciatic nerve and partially corrected the expression of endogenous neurotrophic factors and their receptors, as well as neuroskeletal protein in dorsal root ganglia. These effects translated into normalization of axonal radial growth and significantly improved axonal elongation of regenerating fibers in C-peptide-replaced BB/Wor-rats. The findings in C-peptide replaced type 1 diabetic rats were similar to those previously reported in hyperinsulinemic and iso-hyperglycemic type 2 BB/Z-rats. We conclude that impaired insulin action may be more important than hyperglycemia in suppressing nerve fiber regeneration in type 1 diabetic neuropathy.

Authors+Show Affiliations

Department of Pathology, Wayne State University, School of Medicine and Detroit Medical Center, Detroit, Michigan 48201, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12901702

Citation

Pierson, Christopher R., et al. "Proinsulin C-peptide Replacement in Type 1 Diabetic BB/Wor-rats Prevents Deficits in Nerve Fiber Regeneration." Journal of Neuropathology and Experimental Neurology, vol. 62, no. 7, 2003, pp. 765-79.
Pierson CR, Zhang W, Sima AA. Proinsulin C-peptide replacement in type 1 diabetic BB/Wor-rats prevents deficits in nerve fiber regeneration. J Neuropathol Exp Neurol. 2003;62(7):765-79.
Pierson, C. R., Zhang, W., & Sima, A. A. (2003). Proinsulin C-peptide replacement in type 1 diabetic BB/Wor-rats prevents deficits in nerve fiber regeneration. Journal of Neuropathology and Experimental Neurology, 62(7), 765-79.
Pierson CR, Zhang W, Sima AA. Proinsulin C-peptide Replacement in Type 1 Diabetic BB/Wor-rats Prevents Deficits in Nerve Fiber Regeneration. J Neuropathol Exp Neurol. 2003;62(7):765-79. PubMed PMID: 12901702.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Proinsulin C-peptide replacement in type 1 diabetic BB/Wor-rats prevents deficits in nerve fiber regeneration. AU - Pierson,Christopher R, AU - Zhang,Weixian, AU - Sima,Anders A F, PY - 2003/8/7/pubmed PY - 2003/8/23/medline PY - 2003/8/7/entrez SP - 765 EP - 79 JF - Journal of neuropathology and experimental neurology JO - J. Neuropathol. Exp. Neurol. VL - 62 IS - 7 N2 - We recently reported that early gene responses and expression of cytoskeletal proteins are perturbed in regenerating nerve in type 1 insulinopenic diabetes but not in type 2 hyperinsulinemic diabetes. We hypothesized that these differences were due to impaired insulin action in the former type of diabetes. To test this hypothesis, type 1 diabetic BB/Wor-rats were replaced with proinsulin C-peptide, which enhances insulin signaling without lowering blood glucose. Following sciatic nerve crush injury, early gene responses such as insulin-like growth factor, c-fos, and nerve growth factor were examined longitudinally in sciatic nerve. Neurotrophic factors, their receptors, and beta-tubulin and neurofilament expression were examined in dorsal root ganglia. C-peptide replacement significantly normalized early gene responses in injured sciatic nerve and partially corrected the expression of endogenous neurotrophic factors and their receptors, as well as neuroskeletal protein in dorsal root ganglia. These effects translated into normalization of axonal radial growth and significantly improved axonal elongation of regenerating fibers in C-peptide-replaced BB/Wor-rats. The findings in C-peptide replaced type 1 diabetic rats were similar to those previously reported in hyperinsulinemic and iso-hyperglycemic type 2 BB/Z-rats. We conclude that impaired insulin action may be more important than hyperglycemia in suppressing nerve fiber regeneration in type 1 diabetic neuropathy. SN - 0022-3069 UR - https://www.unboundmedicine.com/medline/citation/12901702/Proinsulin_C_peptide_replacement_in_type_1_diabetic_BB/Wor_rats_prevents_deficits_in_nerve_fiber_regeneration_ L2 - https://academic.oup.com/jnen/article-lookup/doi/10.1093/jnen/62.7.765 DB - PRIME DP - Unbound Medicine ER -