title: Contractile activity of human skeletal muscle cells prevents insulin resistance by inhibiting pro-inflammatory signalling pathways.
abstract: OBJECTIVE
  Obesity is closely associated with muscle insulin resistance and is a major risk factor for the pathogenesis of type 2 diabetes. Regular physical activity not only prevents obesity, but also considerably improves insulin sensitivity and skeletal muscle metabolism. We sought to establish and characterise an in vitro model of human skeletal muscle contraction, with a view to directly studying the signalling pathways and mechanisms that are involved in the beneficial effects of muscle activity.
  
  
  METHODS
  Contracting human skeletal muscle cell cultures were established by applying electrical pulse stimulation. To induce insulin resistance, skeletal muscle cells were incubated with human adipocyte-derived conditioned medium, monocyte chemotactic protein (MCP)-1 and chemerin.
  
  
  RESULTS
  Similarly to in exercising skeletal muscle in vivo, electrical pulse stimulation induced contractile activity in human skeletal muscle cells, combined with the formation of sarcomeres, activation of AMP-activated protein kinase (AMPK) and increased IL-6 secretion. Insulin-stimulated glucose uptake was substantially elevated in contracting cells compared with control. The incubation of skeletal muscle cells with adipocyte-conditioned media, chemerin and MCP-1 significantly reduced the insulin-stimulated phosphorylation of Akt. This effect was abrogated by concomitant pulse stimulation of the cells. Additionally, pro-inflammatory signalling by adipocyte-derived factors was completely prevented by electrical pulse stimulation of the myotubes.
  
  
  CONCLUSIONS
  We showed that the effects of electrical pulse stimulation on skeletal muscle cells were similar to the effect of exercise on skeletal muscle in vivo in terms of enhanced AMPK activation and IL-6 secretion. In our model, muscle contractile activity eliminates insulin resistance by blocking pro-inflammatory signalling pathways. This novel model therefore provides a unique tool for investigating the molecular mechanisms that mediate the beneficial effects of muscle contraction.
authors.affiliation: German Diabetes Center, Auf´m Hennekamp 65, Duesseldorf, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Lambernd
authors.forename: A
authors.initials: A
authors.lastname: Taube
authors.forename: A
authors.initials: A
authors.lastname: Schober
authors.forename: B
authors.initials: B
authors.lastname: Platzbecker
authors.forename: S W
authors.initials: SW
authors.lastname: Görgens
authors.forename: R
authors.initials: R
authors.lastname: Schlich
authors.forename: K
authors.initials: K
authors.lastname: Jeruschke
authors.forename: J
authors.initials: J
authors.lastname: Weiss
authors.forename: K
authors.initials: K
authors.lastname: Eckardt
authors.forename: J
authors.initials: J
authors.lastname: Eckel
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000494:pharmacology; D018925:Chemokines / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D018932:Chemokine CCL2; D018925:Chemokines; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; C478630:RARRES2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D000263:Adenylate Kinase; D005947:Glucose