title: 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men.
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/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) 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 (R(2) = 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 alpha(1) and alpha(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 1/2, but phosphorylation of beta-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.
authors.affiliation: Department of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK. d.j.r.cuthbertson@dundee.ac.uk
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cuthbertson
authors.forename: John A
authors.initials: JA
authors.lastname: Babraj
authors.forename: Kirsteen J W
authors.initials: KJ
authors.lastname: Mustard
authors.forename: Mhairi C
authors.initials: MC
authors.lastname: Towler
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Green
authors.forename: Henning
authors.initials: H
authors.lastname: Wackerhage
authors.forename: Graeme P
authors.initials: GP
authors.lastname: Leese
authors.forename: Keith
authors.initials: K
authors.lastname: Baar
authors.forename: Michaela
authors.initials: M
authors.lastname: Thomason-Hughes
authors.forename: Calum
authors.initials: C
authors.lastname: Sutherland
authors.forename: D Grahame
authors.initials: DG
authors.lastname: Hardie
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rennie
mesh_terms: D055372:AMP-Activated Protein Kinases; D000328:Adult; D000620:Aminoimidazole Carboxamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D003847:Deoxyglucose / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D006003:Glycogen / Q000378:metabolism; D006262:Health; D006728:Hormones / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D007527:Isoenzymes / Q000378:metabolism; D019344:Lactic Acid / Q000097:blood; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012263:Ribonucleosides / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D006728:Hormones; D007328:Insulin; D007527:Isoenzymes; D009097:Multienzyme Complexes; D012263:Ribonucleosides; D019344:Lactic Acid; D000620:Aminoimidazole Carboxamide; C011651:acadesine; D006003:Glycogen; D003847:Deoxyglucose; C526181:PRKAA2 protein, human; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human