title: Uniaxial cyclic stretch-stimulated glucose transport is mediated by a ca-dependent mechanism in cultured skeletal muscle cells.
abstract: OBJECTIVE
  Mechanical stimuli such as stretch increase glucose transport and glycogen metabolism in skeletal muscle. However, the molecular mechanisms involved in the mechanotransduction events are poorly understood. The present study was conducted in order to determine whether the signaling mechanism leading to mechanical stretch-stimulated glucose transport is similar to, or distinct from, the signaling mechanisms leading to insulin- and contraction-stimulated glucose transport in cultured muscle cells.
  
  
  METHODS
  Cultured C2C12 myotubes were stretched, after which the 2-deoxy-D-glucose (2-DG) uptake was measured.
  
  
  RESULTS
  Following cyclic stretch, C2C12 myotubes showed a significant increase in 2-DG uptake, and this effect was not prevented by inhibiting phosphatidylinositol 3-kinase or 5'-AMP-activated protein kinase and by extracellular Ca(2+) chelation. Conversely, the stretch-stimulated 2-DG uptake was completely prevented by dantrolene (an inhibitor of Ca(2+) release from sarcoplasmic reticulum). Furthermore, the stretch-stimulated 2-DG uptake was prevented by the Ca(2+)/calmodulin-dependent kinase inhibitor KN93 which did not prevent the insulin-stimulated 2-DG uptake.
  
  
  CONCLUSIONS
  These results suggest that the effects of stretch-stimulated glucose transport are independent of the insulin-signaling pathway. By contrast, following mechanical stretch in skeletal muscle, the signal transduction pathway leading to glucose transport may require the participation of cytosolic Ca(2+) and Ca(2+)/calmodulin kinase, but not 5'-AMP-activated protein kinase.
authors.affiliation: Program in Physical and Occupational Therapy, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iwata
authors.forename: Kimihide
authors.initials: K
authors.lastname: Hayakawa
authors.forename: Taro
authors.initials: T
authors.lastname: Murakami
authors.forename: Keiji
authors.initials: K
authors.lastname: Naruse
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kawakami
authors.forename: Masumi
authors.initials: M
authors.lastname: Inoue-Miyazu
authors.forename: Louis
authors.initials: L
authors.lastname: Yuge
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Suzuki
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D003620:Dantrolene / Q000494:pharmacology; D003847:Deoxyglucose; D004347:Drug Interactions; D005947:Glucose / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D000077191:Wortmannin; D000096926:Benzenesulfonamides
chemical_list: D000730:Androstadienes; D001596:Benzylamines; D002118:Calcium; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002614:Chelating Agents; D003620:Dantrolene; D003847:Deoxyglucose; D005947:Glucose; D009125:Muscle Relaxants, Central; D026902:Potassium Channel Blockers; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077191:Wortmannin; C072105:KN 93; D000096926:Benzenesulfonamides