C-peptide increases forearm blood flow in patients with type 1 diabetes via a nitric oxide-dependent mechanism

1 Section of Clinical Physiology, Department of Surgical Sciences and 2 Section of Cardiology, Department of Medicine, Karolinska Hospital, S-171 76 Stockholm, Sweden Submitted 2 January 2003 ; accepted in final form 4 June 2003 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. acetylcholine; insulin; N G -monomethyl- L -arginine; sodium nitroprusside; venous occlusion plethysmography Address for reprint requests and other correspondence: B.-L. Johansson, Dept. of Surgical Sciences, Division of Clinical Physiology N1:05, Karolinska Hospital, SE-171 76 Stockholm, Sweden.