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Am J Physiol Endocrinol Metab (June 10, 2003). doi:10.1152/ajpendo.00001.2003
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Submitted on January 2, 2003
Accepted on June 4, 2003

C-Peptide Increases Forearm Blood Flow in Patients with Type 1 Diabetes via a Nitric Oxide-Dependent Mechanism

Bo-Lennart Johansson1*, John Wahren1, and John Pernow2

1 Section of Clinical Physiology, Department of Surgical Sciences, Karolinska Hospital, Stockholm, Sweden
2 Section of Cardiology, Department of Medicine, Karolinska Hospital, Stockholm, Sweden

* To whom correspondence should be addressed. E-mail: Bo-lennart.Johansson{at}ks.se.

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 twice and randomized to administration of intravenous and intra-arterial infusion of C-peptide or placebo. 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%, ns). NOS blockade resulted in a more pronounced reduction in FBF during intravenous C-peptide than during saline infusion (-41 %versus -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 forearm blood flow in Type 1 diabetic patients is mediated via the NO-system, and that C-peptide increases basal NO levels.




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