International Journal of Experimental Diabetes Research 
Volume 2 (2001), Issue 3, Pages 187-193
doi:10.1155/EDR.2001.187

Human C-peptide Dose Dependently Prevents Early Neuropathy in the BB/Wor-rat

W. Zhang,1,3 M. Yorek,4 C. R. Pierson,1,3 Y. Murakawa,1,3 A. Breidenbach,5 and A. A. F. Sima1,2,3

 1Department of Pathology, Wayne State University, 540 E. Canfield Ave, Detroit, MI 48201, USA
2Department of Neurotogy, Wayne State University, Detroit, MI, USA
3Morris Hood Jr. Diabetes Center, Wayne State University, Detroit, MI, USA
4Department of Internal Medicine, University of Iowa, Iowa, IO, USA
5Schwarz Pharma AG, Monheim, Germany
Received 11 April 2001; Revised 31 May 2001; Accepted 2 July 2001

Abstract

In order to explore the neuroprotective and crossspecies activities of.C-peptide on type 1 diabetic neuropathy, spontaneously diabetic BB/W-rats were given increasing doses of human recombinant Cpeptide (hrC-peptide). Diabetic rats received 10, 100, 500, or 1000 μg of hrC-peptide/kg body weight/ day from onset of diabetes. After 2 months of hrC-peptide administration, 100 μg and greater doses completely prevented the nerve conduction defect, which was associated with a significant but incomplete prevention of neural Na+/K+-ATPase activity in diabetic rats with 500 μg or greater C-peptide replacement. Increasing doses of hrC-peptide showed increasing prevention of early structural abnormalities such as paranodal swelling and axonal degeneration and an increasing frequency of regenerating sural nerve fibers. We conclude that hrC-peptide exerts a dose dependent protection on type 1 diabetic neuropathy in rats and that this effect is probably mediated by the partially conserved sequence of the active C-terminal pentapeptide