Research Article

C-peptide improves neuropathy in type 1 diabetic BB/Wor-rats

  1. Weixian Zhang1,3,
  2. Hideki Kamiya1,3,
  3. Karin Ekberg4,
  4. John Wahren4,
  5. Anders A. F. Sima1,2,3,*

Article first published online: 17 JUL 2006

DOI: 10.1002/dmrr.672

Issue

Diabetes/Metabolism Research and Reviews

Diabetes/Metabolism Research and Reviews

Volume 23, Issue 1, pages 63–70, January 2007

Additional Information

How to Cite

Zhang, W., Kamiya, H., Ekberg, K., Wahren, J. and Sima, A. A. F. (2007), C-peptide improves neuropathy in type 1 diabetic BB/Wor-rats. Diabetes Metab. Res. Rev., 23: 63–70. doi: 10.1002/dmrr.672

Author Information

  1. 1

    Departments of Pathology, Wayne State University, School of Medicine, Detroit, MI, USA

  2. 2

    Department of Neurology, Wayne State University, School of Medicine, Detroit, MI, USA

  3. 3

    Morris Hood Jr. Comprehensive Diabetes Center, Wayne State University, School of Medicine, Detroit, MI, USA

  4. 4

    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden

*Department of Pathology, Scott Hall 9275, 540 E. Canfield Ave, Detroit, MI 48201, USA.

Publication History

  1. Issue published online: 28 DEC 2006
  2. Article first published online: 17 JUL 2006
  3. Manuscript Accepted: 7 JUN 2006
  4. Manuscript Revised: 6 JUN 2006
  5. Manuscript Received: 3 APR 2006

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Keywords:

  • BB/Wor-rats;
  • C-peptide;
  • neuropathy;
  • nerve conduction velocity;
  • morphometry

Abstract

Background

The spontaneously diabetic BB/Wor-rat is a close model of human type 1 diabetes and develops diabetic polyneuropathy (DPN) similar to that seen in type 1 patients. Here we examine the therapeutic effects of C-peptide, delivered as continuous infusion or once daily subcutaneous injections on established DPN.

Methods

Diabetic rats were treated from four to seven months duration of diabetes with full continuous replacement dose of rat C-peptide via (a) osmopumps (OS), (b) full replacement dose (HSC) or (c) one-third of full replacement dose (LSC) by once daily injections.

Results

Diabetic rats treated with OS showed improvements in motor nerve conduction velocity (p < 0.001), sural nerve myelinated fibre number (p < 0.005), size (p < 0.05), axonal area (p < 0.001), regeneration (p < 0.001) and overall neuropathy score (p < 0.001). The progressive decline in sensory nerve conduction velocity was fully prevented. The frequencies of Wallerian degeneration were decreased (p < 0.005). HSC-treated rats showed prevention of further progression of DPN (p < 0.001), whereas LSC-treated rats showed a milder progression of DPN (p < 0.001) compared to untreated rats as assessed by neuropathy score.

Conclusion

We conclude that (1) C-peptide is effective in the treatment of established DPN, (2) its effect is dose-dependent and (3) replacement by continuous infusion is the most effective administration of C-peptide. Copyright © 2006 John Wiley & Sons, Ltd.

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