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Diabetes 52:1812-1817, 2003
© 2003 by the American Diabetes Association, Inc.

Effects of Proinsulin C-Peptide in Experimental Diabetic Neuropathy

Vascular Actions and Modulation by Nitric Oxide Synthase Inhibition

Mary A. Cotter1, Karin Ekberg2, John Wahren2, and Norman E. Cameron1

1 Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Scotland, U.K
2 Department of Surgical Sciences, Section of Clinical Physiology, Karolinska Institutet, Stockholm, Sweden

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.

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


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