Effects of proinsulin C-peptide in experimental diabetic neuropathy: vascular actions and modulation by nitric oxide synthase inhibition

Mary Anne Cotter, K. Ekberg, J. Wahren, Norman E Cameron

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

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 N-G-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.

Original languageEnglish
Pages (from-to)1812-1817
Number of pages5
JournalDiabetes
Volume52
Issue number7
DOIs
Publication statusPublished - Jul 2003

Keywords

  • ALDOSE REDUCTASE INHIBITION
  • PERIPHERAL-NERVE CONDUCTION
  • K+-ATPASE ACTIVITY
  • RAT SCIATIC-NERVE
  • BLOOD-FLOW
  • NA+,K+-ATPASE ACTIVITY
  • HYPOXIC RESISTANCE
  • POLYOL PATHWAY
  • DYSFUNCTION
  • DEFICITS

Cite this

Effects of proinsulin C-peptide in experimental diabetic neuropathy: vascular actions and modulation by nitric oxide synthase inhibition. / Cotter, Mary Anne; Ekberg, K.; Wahren, J.; Cameron, Norman E.

In: Diabetes, Vol. 52, No. 7, 07.2003, p. 1812-1817.

Research output: Contribution to journalArticle

Cotter, Mary Anne ; Ekberg, K. ; Wahren, J. ; Cameron, Norman E. / Effects of proinsulin C-peptide in experimental diabetic neuropathy: vascular actions and modulation by nitric oxide synthase inhibition. In: Diabetes. 2003 ; Vol. 52, No. 7. pp. 1812-1817.
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