Diabetologia

, Volume 44, Issue 7, pp 889–897 | Cite as

C-peptide prevents and improves chronic Type I diabetic polyneuropathy in the BB/Wor rat

  • A. A. F. Sima
  • W. Zhang
  • K. Sugimoto
  • D. Henry
  • Z. Li
  • J. Wahren
  • G. Grunberger
Article

Abstract

Aims/hypothesis. Insulin and C-peptide exert neuroprotective effects and are deficient in Type I (insulin-dependent) diabetes mellitus but not in Type II (non-insulin-dependent) diabetes mellitus. These studies were designed to test the preventive and interventional effects of C-peptide replacement on diabetic polyneuropathy in the Type I diabetic BB/Wor rat. Methods. Diabetic BB/Wor rats were replaced with rat C-peptide from onset of diabetes and between 5 and 8 months of diabetes. They were examined at 2 and 8 months and compared to non-C-peptide replaced BB/Wor rats, Type II diabetic (non-C-peptide deficient) BB/Z rats and non-diabetic control rats. Animals were monitored as to hyperglycaemia and nerve conduction velocity (NCV). Acute changes such as neural Na+/K+-ATPase and paranodal swelling were examined at 2 months, morphometric and teased fiber analyses were done at 8 months. Results. C-peptide replacement for 2 months in Type I diabetic rats prevented the acute NCV defect by 59 % (p < 0.005), the neural Na+/K+-ATPase defect by 55 % (p < 0.001) and acute paranodal swelling by 61 % (p < 0.001). Eight months of C-peptide replacement prevented the chronic nerve conduction defect by 71 % (p < 0.001) and totally prevented axoglial dysjunction (p < 0.001) and paranodal demyelination (p < 0.001). C-peptide treatment from 5 to 8 months showed a 13 % (p < 0.05) improvement in NCV, a 33 % (p < 0.05) improvement in axoglial dysjunction, normalization (p < 0.001) of paranodal demyelination, repair of axonal degeneration (p < 0.01), and a fourfold (p < 0.001) increase in nerve fibre regeneration. Conclusion/interpretation. C-peptide replacement of Type I BB/Wor-rats partially prevents acute and chronic metabolic, functional and structural changes that separate Type I diabetic polyneuropathy from its Type II counterpart suggesting that C-peptide deficiency plays a pathogenetic role in Type I diabetic polyneuropathy. [Diabetologia (2001) 44: 889–897]

Keywords Diabetic neuropathy C-peptide Na+/K+-ATPase nerve conduction velocity morphometry. 

Copyright information

© Springer-Verlag Berlin Heidelberg 2001

Authors and Affiliations

  • A. A. F. Sima
    • 1
  • W. Zhang
    • 1
  • K. Sugimoto
    • 1
  • D. Henry
    • 3
  • Z. Li
    • 2
  • J. Wahren
    • 4
  • G. Grunberger
    • 2
  1. 1.From the Department of Pathology, Wayne State University, Detroit, Michigan, USAUS
  2. 2.Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan, USAUS
  3. 3.Department of Physiology, Michigan State University, East Lansing, Michigan, USAUS
  4. 4.Department of Clinical Physiology, Karolinska Hospital, Stockholm, SwedenSE

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