title: C-peptide increases forearm blood flow in patients with type 1 diabetes via a nitric oxide-dependent mechanism.
abstract: Proinsulin C-peptide has been shown to increase muscle blood flow in type 1 diabetic patients. The underlying mechanism is not fully understood. The aim of this study was to evaluate if the vasodilator effect of C-peptide is mediated by nitric oxide (NO). Eleven type 1 diabetic patients were studied two times and randomized to administration of intravenous and intra-arterial infusion of C-peptide or saline. Forearm blood flow (FBF) was measured by venous occlusion plethysmography during infusion of C-peptide or saline before, during, and after NO synthase (NOS) blockade. Endothelium-dependent and -independent vasodilatation was evaluated by administration of acetylcholine and sodium nitroprusside, respectively. FBF increased by 35% during intravenous C-peptide (P < 0.01) but not during saline infusion (-2%, not significant). NOS blockade resulted in a more pronounced reduction in FBF during intravenous C-peptide than during saline infusion (-41 vs. -26%, P < 0.05). Intra-arterial C-peptide failed to increase FBF during NOS blockade. However, when C-peptide was given after the recovery from NOS blockade, FBF rose by 30% (P < 0.001). The vasodilator effects of acetylcholine and nitroprusside were not influenced by C-peptide. It is concluded that the stimulatory effect of C-peptide on FBF in type 1 diabetic patients is mediated via the NO system and that C-peptide increases basal endothelial NO levels.
authors.affiliation: Department of Surgical Sciences, Division of Clinical Physiology N1:05, Karolinska Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Bo-Lennart
authors.initials: BL
authors.lastname: Johansson
authors.forename: John
authors.initials: J
authors.lastname: Wahren
authors.forename: John
authors.initials: J
authors.lastname: Pernow
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D002096:C-Peptide / Q000008:administration & dosage*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000503:physiopathology*; D005542:Forearm / Q000098:blood supply* / Q000503:physiopathology*; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage; D019323:omega-N-Methylarginine / Q000494:pharmacology*
chemical_list: D002096:C-Peptide; D007328:Insulin; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine