5-Aminoimidazole-4-Carboxamide 1-β-d-Ribofuranoside Acutely Stimulates Skeletal Muscle 2-Deoxyglucose Uptake in Healthy Men

  1. Daniel J. Cuthbertson1,
  2. John A. Babraj2,
  3. Kirsteen J.W. Mustard3,
  4. Mhairi C. Towler4,
  5. Kevin A. Green3,
  6. Henning Wackerhage4,
  7. Graeme P. Leese1,
  8. Keith Baar3,
  9. Michaela Thomason-Hughes3,
  10. Calum Sutherland5,
  11. D. Grahame Hardie3 and
  12. Michael J. Rennie6
  1. 1Department of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland
  2. 2School of Life Sciences, Heriot Watt University, Edinburgh, Scotland
  3. 3Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee, Scotland
  4. 4College of Life Sciences and Medicine, University of Aberdeen, Aberdeen, Scotland
  5. 5Department of Pharmacology and Neurosciences, University of Dundee, Dundee, Scotland
  6. 6School of Biomedical Sciences, Graduate Entry Medical School, University of Nottingham, Derby City Hospital, Derby, U.K
  1. Address correspondence and reprint requests to Dr. Daniel Cuthbertson, Department of Medicine, Ninewells Hospital and Medical School, Dundee, Scotland DD1 9SY. E-mail: d.j.r.cuthbertson{at}dundee.ac.uk

Abstract

Activation of AMP-activated protein kinase (AMPK) in rodent muscle by exercise, metformin, 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside (AICAR), and adiponectin increases glucose uptake. The aim of this study was to determine whether AICAR stimulates muscle glucose uptake in humans. We studied 29 healthy men (aged 26 ± 8 years, BMI 25 ± 4 kg/m2 [mean ± SD]). Rates of muscle 2-deoxyglucose (2DG) uptake were determined by measuring accumulation of total muscle 2DG (2DG and 2DG-6-phosphate) during a primed, continuous 2DG infusion. The effects of AICAR and exercise on muscle AMPK activity/phosphorylation and 2DG uptake were determined. Whole-body glucose disposal was compared before and during AICAR with the euglycemic-hyperinsulinemic clamp. Muscle 2DG uptake was linear over 9 h (R2 = 0.88 ± 0.09). After 3 h, 2DG uptake increased 2.1 ± 0.8- and 4.7 ± 1.7-fold in response to AICAR or bicycle exercise, respectively. AMPK α1 and α2 activity or AMPK phosphorylation was unchanged after 20 min or 3 h of AICAR, but AMPK phosphorylation significantly increased immediately and 3 h after bicycle exercise. AICAR significantly increased phosphorylation of extracellular signal–regulated kinase 1/2, but phosphorylation of β-acetyl-CoA carboxylase, glycogen synthase, and protein kinase B or insulin receptor substrate-1 level was unchanged. Mean whole-body glucose disposal increased by 7% with AICAR from 9.3 ± 0.6 to 10 ± 0.6 mg · kg−1 · min−1 (P < 0.05). In healthy people, AICAR acutely stimulates muscle 2DG uptake with a minor effect on whole-body glucose disposal.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 18 May 2007. DOI: 10.2337/db06-1716.

    D.J.C. and J.A.B. contributed equally to this work.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted May 11, 2007.
    • Received December 8, 2006.
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  1. Published online before print May 18, 2007, doi: 10.2337/db06-1716 Diabetes August 2007 vol. 56 no. 8 2078-2084
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