5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men

Daniel J. Cuthbertson, John A. Babraj, Kirsteen J.W. Mustard, Mhairi C. Towler, Kevin A. Green, Henning Wackerhage, Graeme P. Leese, Keith Barr, Michaela Thomason-Hughes, Calum Sutherland, D. Graeme Hardie, Michael J. Rennie

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Abstract

Activation of AMP-activated protein kinase (AMPK) in rodent muscle by exercise, metformin, 5-aminoimidazole-4-carboxamide 1-beta-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 x kg-1 x min-1 (P < 0.05). In healthy people, AICAR acutely stimulates muscle 2DG uptake with a minor effect on whole-body glucose disposal.
Original languageEnglish
Pages (from-to)2078-2084
Number of pages7
JournalDiabetes
Volume56
Issue number8
Early online date18 May 2007
DOIs
Publication statusPublished - Aug 2007
Externally publishedYes

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Cuthbertson, D. J., Babraj, J. A., Mustard, K. J. W., Towler, M. C., Green, K. A., Wackerhage, H., Leese, G. P., Barr, K., Thomason-Hughes, M., Sutherland, C., Hardie, D. G., & Rennie, M. J. (2007). 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men. Diabetes, 56(8), 2078-2084. https://doi.org/10.2337/db06-1716