Uniaxial cyclic stretch-stimulated glucose transport is mediated by a Ca2+-dependent mechanism in cultured skeletal muscle cells

Masahiro Iwata, Kimihide Hayakawa, Taro Murakami, Keiji Naruse, Keisuke Kawakami, Masumi Inoue-Miyazu, Louis Yuge, Shigeyuki Suzuki

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


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 Ca2+ chelation. Conversely, the stretch-stimulated 2-DG uptake was completely prevented by dantrolene (an inhibitor of Ca2+ release from sarcoplasmic reticulum). Furthermore, the stretch-stimulated 2-DG uptake was prevented by the Ca2+/ 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 Ca2+ and Ca 2+/calmodulin kinase, but not 5′-AMP-activated protein kinase.

Original languageEnglish
Pages (from-to)159-168
Number of pages10
Issue number3
Publication statusPublished - Jul 2007


  • Glucose uptake
  • Intracellular Ca concentration
  • Mechanical stretch
  • Myotube

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology


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