Uniaxial Cyclic Stretch-Stimulated Glucose Transport Is Mediated by a Ca²⁺-Dependent Mechanism in Cultured Skeletal Muscle Cells
Masahiro Iwata^a, Kimihide Hayakawa^b, Taro Murakami^c, Keiji Naruse^d, Keisuke Kawakami^a, Masumi Inoue-Miyazu^a, Louis Yuge^e, Shigeyuki Suzuki<sup>a

a</sup>Program in Physical and Occupational Therapy, Nagoya University Graduate School of Medicine, and
^bICORP/SORST Cell Mechanosensing, Japan Science and Technology Agency, Nagoya,
^cDepartment of Nutrition, Faculty of Wellness, Chukyo Women's University, Ohbu,
^dDepartment of Cardiovascular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, and
^eDivision of Bio-Environment Adaptation Sciences, Graduate School of Health Sciences, Hiroshima University, Hiroshima, Japan

Pathobiology 2007;74:159-168 (DOI: 10.1159/000103375)

  Key Words

  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 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 Ca²⁺/calmodulin kinase, but not 5'-AMP-activated protein kinase.