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- Title
5-Aminoimidazole-4-Carboxamide 1-β-D-Ribofuranoside Acutely Stimulates Skeletal Muscle 2-Deoxyglucose Uptake in Healthy Men.
- Authors
Cuthbertson, Daniel J.; Babraj, John A.; Mustard, Kirsteen J. W.; Towler, Mhairi C.; Green, Kevin A.; Wackerhage, Henning; Leese, Graeme P.; Baar, Keith; Thomason-Hughes, Michaela; Sutherland, Calum; Hardie, D. Grahame; Rennie, Michael J.
- 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 α[sub 1] 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 ½, 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. Diabetes 56:2078-2084, 2007
- Subjects
MUSCULOSKELETAL system; ADENOSINE monophosphate; PROTEIN kinases; PHOSPHORYLATION; BLOOD sugar; INSULIN receptors
- Publication
Diabetes, 2007, Vol 56, Issue 8, p2078
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db06-1716