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Intra-arterial AICA-riboside administration induces NO-dependent vasodilation in vivo in human skeletal muscle
Department of General Internal Medicine, Radboud University, Nijmegen Medical Centre, Nijmegen, Netherlands & Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.
Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, Netherlands.ORCID iD: 0000-0003-4235-0634
Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, Netherlands & Department of Human Movement Sciences, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, Netherlands.
Department of General Internal Medicine, Radboud University, Nijmegen Medical Centre, Nijmegen, Netherlands & Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.
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2009 (English)In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 297, no 3, E759-E766 p.Article in journal (Refereed) Published
Abstract [en]

In animal models, administration of the adenosine analog AICA-riboside has shown beneficial effects on ischemia-reperfusion injury and glucose homeostasis. The vascular and/or metabolic effects of AICA-riboside administration in humans remain to be established. AICA-riboside was infused intra-arterially in four different dosages up to 8 mg·min-1·dl-1 in 24 healthy subjects. Forearm blood flow (FBF) and glucose uptake and plasma glucose, free fatty acid, and AICA-riboside concentrations were assessed. We also combined AICAriboside infusion (2 mg·min-1·dl -1) with the intra-arterial administration of the adenosine receptor antagonist caffeine (90 μg·min-1·dl-1; n = 6) and with the endothelial NO synthase inhibitor L-NMMA (0.4 mg·min-1·dl-1; n = 6). Additional in vitro experiments were performed to explain our in vivo effects of AICA-riboside in humans. AICA-riboside increased FBF dose dependently from 2.0 ± 0.2 to 13.2 ± 1.9 ml·min-1·dl-1 maximally (P < 0.05 for all dosages). The latter was not reduced by caffeine administration but was significantly attenuated by L-NMMA infusion. Despite high plasma AICA-riboside concentrations, forearm glucose uptake did not change. In vitro experiments showed rapid uptake of AICA-riboside by the equilibrative nucleoside transporter in erythrocytes and subsequent phosphorylation to AICA-ribotide. We conclude that AICA-riboside induces a potent vasodilator response in humans that is mediated by NO. Despite high local plasma concentrations, AICA-riboside does not increase skeletal muscle glucose uptake. Copyright © 2009 the American Physiological Society.

Place, publisher, year, edition, pages
Bethesda, MD: American Physiological Society , 2009. Vol. 297, no 3, E759-E766 p.
Keyword [en]
5-Aminoimidazole-4-carboxamide, Forearm blood flow, Forearm glucose uptake, Nitric oxide
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:hh:diva-26614DOI: 10.1152/ajpendo.00141.2009ISI: 000269063000021PubMedID: 19602584Scopus ID: 2-s2.0-69049120920OAI: oai:DiVA.org:hh-26614DiVA: diva2:750423
Note

This work was supported by a grant from the Dutch Diabetes Foundation.

Available from: 2014-09-29 Created: 2014-09-29 Last updated: 2015-09-29Bibliographically approved

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