title: C-peptide has no effect on forearm blood flow during local hyperinsulinaemia in healthy humans.
abstract: BACKGROUND
  C-peptide increases forearm blood flow (FBF) in patients with Type 1 diabetes, probably by interaction with insulin, but not in healthy subjects. It is unclear if the vasodilating effect is sealed at normal fasting insulin concentrations.
  
  
  METHODS
  The effects of C-peptide alone and during local hyperinsulinaemia were studied in healthy young men. Subjects received intra-arterial insulin at 6 pmol min-1 (low dose) or placebo for 60 min with subsequent coinfusion of C-peptide at increasing doses of 2-60 pmol min-1 in a double-blind crossover study (n = 8). In control experiments insulin at 30 pmol min-1 (high dose) was coinfused with C-peptide (n = 3). FBF was measured by strain-gauge plethysmography.
  
  
  RESULTS
  Placebo had no effect on FBF (mean percentage change from baseline at 50 min -3.1%, 95% confidence interval [CI]-14.9, + 8.7). Insulin infusion slightly enhanced FBF by + 10.2% (95% CI -6.8, + 27.2; low dose) and + 17.6% (95% CI -38.8, + 74.0; high dose), respectively. The mean individual difference of the change in FBF between low-dose insulin and placebo was + 13.3% (95% CI -6.0, + 32.7; P = NS). Infusion of C-peptide increased local C-peptide concentrations from 1.8 +/- 0.1 ng ml-1 to 6.1 +/- 2.8 ng ml-1, but had no effect on FBF during placebo or hyperinsulinaemia (mean difference vs low dose insulin -16.0%, 95% CI -38.9, + 6.9).
  
  
  CONCLUSIONS
  The vasodilating effect of C-peptide seen in Type 1 diabetes is not detectable during fasting or hyperinsulinaemia in the forearm vasculature of healthy subjects. This suggests saturation of its vasodilating potency at insulin concentrations within the normal or in the supraphysiological range.
authors.affiliation: Department of Clinical Pharmacology, University of Vienna, Vienna, Austria.
authors.forename: Herbert
authors.initials: H
authors.lastname: Langenberger
authors.forename: Georg
authors.initials: G
authors.lastname: Schaller
authors.forename: Johannes
authors.initials: J
authors.lastname: Pleiner
authors.forename: Friedrich
authors.initials: F
authors.lastname: Mittermayer
authors.forename: Michaela
authors.initials: M
authors.lastname: Bayerle-Eder
authors.forename: Michael
authors.initials: M
authors.lastname: Wolzt
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D002096:C-Peptide / Q000494:pharmacology*; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000097:blood*; D008297:Male; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D002096:C-Peptide; D007328:Insulin; D014665:Vasodilator Agents