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This Article Full Text Full Text (PDF) All Versions of this Article: 296/5/E1042    most recent 90811.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Babraj, J. A. Articles by Cuthbertson, D. J. Search for Related Content PubMed PubMed Citation Articles by Babraj, J. A. Articles by Cuthbertson, D. J.

Blunting of AICAR-induced human skeletal muscle glucose uptake in type 2 diabetes is dependent on age rather than diabetic status

¹Department of Translational Biomedicine, Heriot Watt University, Edinburgh; ²Division of Molecular Physiology, College of Life Sciences; ³Department of Pharmacology and Neurosciences, University of Dundee; ⁴Medical Research Council Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee; ⁵School of Biomedical Sciences, Graduate Entry Medical School, University of Nottingham, Derby City Hospital, Derby; ⁶Department of Diabetes, Ninewells Hospital and Medical School, Dundee; and ⁷Department of Diabetes, Clinical Sciences Centre, University Hospital Aintree, Liverpool

Submitted 1 October 2008 ; accepted in final form 22 January 2009

We demonstrated previously that, in healthy young men, 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) stimulates human muscle 2-deoxyglucose (2DG) uptake without detectable activation of muscle AMP-activated protein kinase (AMPK) but with extracellular-regulated kinase 1/2 (ERK1/2) activation. We tested whether AICAR stimulates muscle 2DG uptake in healthy older patients with or without type 2 diabetes (T2D). Six healthy young subjects (23 ± 3 yr, BMI 25 ± 2 kg/m^–2; means ± SE), eight older subjects (59 ± 4 yr, BMI 28 ± 2 kg/m^–2), and eight subjects with T2D (62 ± 4 yr, BMI 27 ± 2 kg/m^–2) received a 6-h 2DG infusion (prime 10 mg/kg, 6 mg·kg^–1·h^–1) and AICAR (10 or 20 mg·kg^–1·h^–1) from 3 to 6 h. Quadriceps biopsies were taken at 0, 3, and 6 h. We determined 1) 2DG uptake, 2) total AMPK activity, AMPK, acetyl-CoA carboxylase (ACC), and AS160 phosphorylation, and 3) ERK1/2 phosphorylation. Ten milligrams per kilogram per hour AICAR increased 2DG uptake by 2.9 ± 0.7-fold in young men (P < 0.001), 1.8 ± 0.2-fold in older men (P < 0.01), and 1.6 ± 0.1-fold in men with T2D; 20 mg·kg^–1·h^–1 AICAR increases were 2.5 ± 0.1-fold (older men, P < 0.001) and 2.2 ± 0.2-fold (men with T2D, P < 0.001). At 3-h AMPK activity and AMPK, ACC and AS160 phosphorylation were unchanged, but ERK1/2 phosphorylation increased at both AICAR doses. The fold changes of ERK1/2 phosphorylation and 2DG uptake closely correlated (R² = 0.55, P = 0.003). AICAR stimulates muscle 2DG uptake in T2D to the same extent as in healthy age-matched controls, but there is an age-related reduction.

5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside; adenosine 5'-monophosphate-activated protein kinase; extracellular-signal-regulated kinase 1/2

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