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AICAR acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men.

¹Department of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, DD1 9SY;
²School of Life Sciences, Heriot Watt University, Edinburgh, Scotland, EH14 4AS;
³Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee, Scotland, DD1 5EH;
⁴College of Life Sciences & Medicine, University of Aberdeen, Aberdeen, Scotland, AB25 2ZD;
⁵Department of Pharmacology and Neurosciences, University of Dundee, Dundee, Scotland, DD1 9SY;
⁶School of Biomedical Sciences, Graduate Entry Medical School, University of Nottingham, Derby City Hospital, DE22 3DT

Correspondence: d.j.r.cuthbertson{at}dundee.ac.uk

Key Words: skeletal muscle • AMPK • glucose uptake • AICAR • ERK1/2

Objective:Activation of AMP-activated protein kinase (AMPK) in rodent muscle, by exercise, metformin, 5-aminoimidazole-4-carboxamide 1-ß-D-ribofuranoside (AICAR) and adiponectin, increases glucose uptake. The aim of the study was to determine whether AICAR stimulates muscle glucose uptake in humans.

Research Design and Methods:We studied twenty nine healthy men (26 ± 8 y, BMI 25 ± 4 kg.m^–2; mean ± SD). Rates of muscle 2-deoxyglucose (2DG) uptake were determined by measuring accumulation of total muscle 2DG (2DG and 2DG-6-phosphate, 2DG6P) during a primed, continuous 2DG infusion. The effects of AICAR and exercise on muscle AMPK activity/phosphorylation and 2DG uptake were determined. Whole body insulin sensitivity was compared before and during AICAR with the euglycaemic, hyperinsulinaemic clamp.

Results:Muscle 2DG uptake was linear over 9 h (R²= 0.89 ± 0.08). 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-₁ and ₂ 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 (ERK1/2), but phosphorylation of ß--acetylCoA carboxylase (ß--ACC), glycogen synthase (GS), protein kinase B (PKB) or insulin receptor substrate (IRS1) 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).

Conclusion:In healthy people, AICAR acutely stimulates muscle 2DG uptake with a minor effect on whole body glucose disposal.

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