title: Enhanced Muscle Insulin Sensitivity After Contraction/Exercise Is Mediated by AMPK.
abstract: Earlier studies have demonstrated that muscle insulin sensitivity to stimulate glucose uptake is enhanced several hours after an acute bout of exercise. Using AICAR, we recently demonstrated that prior activation of AMPK is sufficient to increase insulin sensitivity in mouse skeletal muscle. Here we aimed to determine whether activation of AMPK is also a prerequisite for the ability of muscle contraction to increase insulin sensitivity. We found that prior in situ contraction of m. extensor digitorum longus (EDL) and treadmill exercise increased muscle and whole-body insulin sensitivity in wild-type (WT) mice, respectively. These effects were not found in AMPKα1α2 muscle-specific knockout mice. Prior in situ contraction did not increase insulin sensitivity in m. soleus from either genotype. Improvement in muscle insulin sensitivity was not associated with enhanced glycogen synthase activity or proximal insulin signaling. However, in WT EDL muscle, prior in situ contraction enhanced insulin-stimulated phosphorylation of TBC1D4 Thr649and Ser711Such findings are also evident in prior exercised and insulin-sensitized human skeletal muscle. Collectively, our data suggest that the AMPK-TBC1D4 signaling axis is likely mediating the improved muscle insulin sensitivity after contraction/exercise and illuminates an important and physiologically relevant role of AMPK in skeletal muscle.
authors: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.|Section of Integrative Physiology, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Rasmus
authors: R
authors: Kjøbsted
authors: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
authors: Nanna
authors: N
authors: Munk-Hansen
authors: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
authors: Jesper B
authors: JB
authors: Birk
authors: INSERM, U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors: Marc
authors: M
authors: Foretz
authors: INSERM, U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors: Benoit
authors: B
authors: Viollet
authors: Integrative Physiology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors: Marie
authors: M
authors: Björnholm
authors: Section of Integrative Physiology, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|Integrative Physiology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors: Juleen R
authors: JR
authors: Zierath
authors: Section of Integrative Physiology, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Jonas T
authors: JT
authors: Treebak
authors: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark jwojtaszewski@nexs.ku.dk.
authors: Jørgen F P
authors: JF
authors: Wojtaszewski
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D066298:In Vitro Techniques; D007333:Insulin Resistance / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism*; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D015398:Signal Transduction
chemical_list: D020690:GTPase-Activating Proteins; C505647:Tbc1d4 protein, mouse; D006003:Glycogen; D006006:Glycogen Synthase; C548179:Prkaa1 protein, mouse; C534978:Prkaa2 protein, mouse; C526221:Prkag3 protein, mouse; D055372:AMP-Activated Protein Kinases; D005947:Glucose