title: The alpha-subunit of AMPK is essential for submaximal contraction-mediated glucose transport in skeletal muscle in vitro.
abstract: AMP-activated protein kinase (AMPK) is a key signaling protein in the regulation of skeletal muscle glucose uptake, but its role in mediating contraction-induced glucose transport is still debated. The effect of contraction on glucose transport is impaired in EDL muscle of transgenic mice expressing a kinase-dead, dominant negative form of the AMPKalpha(2) subunit (KD-AMPKalpha(2) mice). However, maximal force production is reduced in this muscle, raising the possibility that the defect in glucose transport was due to a secondary decrease in force production and not impaired AMPKalpha(2) activity. Generation of force-frequency curves revealed that muscle force production is matched between wild-type (WT) and KD-AMPKalpha(2) mice at frequencies < or =50 Hz. Moreover, AMPK activation is already maximal at 50 Hz in muscles of WT mice. When EDL muscles from WT mice were stimulated at a frequency of 50 Hz for 2 min (200-ms train, 1/s, 30 volts), contraction caused an approximately 3.5-fold activation of AMPKalpha(2) activity and an approximately 2-fold stimulation of glucose uptake. Conversely, whereas force production was similar in EDL of KD-AMPKalpha(2) animals, no effect of contraction was observed on AMPKalpha(2) activity, and glucose uptake stimulation was reduced by 50% (P < 0.01) As expected, 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranosyl 5'-monophosphate (AICAR) caused a 2.3-fold stimulation of AMPKalpha(2) activity and a 1.7-fold increase in glucose uptake in EDL from WT mice, whereas no effect was detected in muscle from KD-AMPKalpha(2) mice. These data demonstrate that AMPK activation is essential for both AICAR and submaximal contraction-induced glucose transport in skeletal muscle but that AMPK-independent mechanisms are also involved.
authors.affiliation: Department of Anatomy, Laval University Hospital Research Center, Quebec, Canada.
authors.forename: Natalie
authors.initials: N
authors.lastname: Lefort
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: St-Amand
authors.forename: Sébastien
authors.initials: S
authors.lastname: Morasse
authors.forename: Claude H
authors.initials: CH
authors.lastname: Côté
authors.forename: André
authors.initials: A
authors.lastname: Marette
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010812:Physical Stimulation; D012265:Ribonucleotides / Q000494:pharmacology
chemical_list: D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; C534978:Prkaa2 protein, mouse; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D005947:Glucose