Effects of Proinsulin C-Peptide in Experimental Diabetic Neuropathy

Vascular Actions and Modulation by Nitric Oxide Synthase Inhibition

  1. Mary A. Cotter1,
  2. Karin Ekberg2,
  3. John Wahren2 and
  4. Norman E. Cameron1
  1. 1Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Scotland, U.K
  2. 2Department of Surgical Sciences, Section of Clinical Physiology, Karolinska Institutet, Stockholm, Sweden
  1. Address correspondence and reprint requests to Norman E. Cameron, Dphil, Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, U.K. E-mail: n.e.cameron{at}abdn.ac.uk


Proinsulin C-peptide treatment can partially prevent nerve dysfunction in type 1 diabetic rats and patients. This could be due to a direct action on nerve fibers or via vascular mechanisms as C-peptide stimulates the nitric oxide (NO) system and NO-mediated vasodilation could potentially account for any beneficial C-peptide effects. To assess this further, we examined neurovascular function in streptozotocin-induced diabetic rats. After 6 weeks of diabetes, rats were treated for 2 weeks with C-peptide to restore circulating levels to those of nondiabetic controls. Additional diabetic groups were given C-peptide with NO synthase inhibitor NG-nitro-l-arginine (l-NNA) co-treatment or scrambled C-peptide. Diabetes caused 20 and 16% reductions in sciatic motor and saphenous sensory nerve conduction velocity, which were 62 and 78% corrected, respectively, by C-peptide. l-NNA abolished C-peptide effects on nerve conduction. Sciatic blood flow and vascular conductance were 52 and 41%, respectively, reduced by diabetes (P < 0.001). C-peptide partially (57–66%) corrected these defects, an effect markedly attenuated by l-NNA co-treatment. Scrambled C-peptide was without effect on nerve conduction or perfusion. Thus, C-peptide replacement improves nerve function in experimental diabetes, and the data are compatible with the notion that this is mediated by a NO-sensitive vascular mechanism.


    • Accepted March 26, 2003.
    • Received December 18, 2002.
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