Molecular mechanisms for regulation of glucose metabolism in skeletal muscle cells by biomechanical stress.
| Project/Area Number |
18590064
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Iwate Medical University (2007)
University of Shizuoka (2006) |
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Principal Investigator |
NAKAYAMA Koichi Iwate Medical University, School of Pharmaceutical Sciences, Department of Molecular and Cellular Pharmacology, Ph.D. Professor (50112769)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIKAWA Tomohisa University of Shizuoka, Graduate School of Pharmaceutical Sciences, Department of Molecular Pharmacology, Ph.D. Professor (10201914)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,980,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | mechanotransduction / cell signaling / exercise / skeletal muscle / glucose metabolism / mechanostress / pharmacology / metabolic syndrome / 生理学 / 糖尿病 |
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| Research Abstract |
Muscle contraction is accompanied by passive stretching or deformation of cells and tissues. The present research project aimed to clarify molecular mechanisms involved in glucose transporter 4 (GLUT4) translocation and glucose uptake in skeletal muscles of mice in response to passive stretching. The following results were obtained :
1. Passive stretching mainly induced GLUT4 translocation from an intracellular membrane to a plasma membrane and accelerated glucose uptake in hindlimb muscles, whereas electrical stimulation, which mimics physical exercise in vivo, and insulin each induced GLUT4 translocation from an intracellular membrane to plasma membrane and to transverse tubules, along with subsequent glucose uptake.
2. Mechanical stretching increased phosphorylation of protein kinase B (Akt) and p38 mitogen-activated protein kinase (p38 MAPK), but it had no apparent effect on the activity of AMP-activated protein kinase (AMPK), a metabolic sensor molecule.
3. Electrical stimulation, on the other hand, augmented the activity of not only AMPK but also phosphorylation of Akt and p38 MAPK.
4. We established a preparation of micro bundles of gastrocnemius muscle in mice for further elucidation of molecular mechanisms.
5. Mechanical stretching translocated phosphatidylinositol kinase (PI3K) from cytosol to caveolin-3 near caveolae of plasma membrane when assessed by immunostaining assay and confocal laser microscopy.
The results suggest that passive stretching activates PI3K-Akt pathway in AMPK- and insulin-independent manners, which produces translocation of GLUT4 and the glucose uptake. This means that passive stretching could alternatively activate intracellular signalings mediated by insulin without insulin. Furthermore, the study indicates a new molecular mechanism for glucose uptake accompanied with exercise, which will promote the development of a novel strategy/drug for regulation of glucose metabolism in health and disease.
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Report
(3 results)
Research Products
(95 results)
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[Journal Article] Effects of olmesartan,an AT1 receptor antagonist,on hypoxia-induced activation of ERKI/2 and pro-inflammatory signals in the mouse lung2006
Author(s)
Yoshiyuki Tanabe, Yuki Morikawa, Takao Kato, Satoshi Kanai, Taichi Watakabe, Ami Nishijima, Hijiri Iwata, Kaori Isobe, Mayumi Ishizaki, Koichi Nakayama
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Journal Title
Naunyn-Schmiedeberg's Arch.Pharmacol 374
Pages: 235-248
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Involvement of stretch-activated cation channels in hypotonically induced insulin secretion in rat pancreatic 13-cells2006
Author(s)
Miki, Takii, Tomohisa, Ishikawa, Hidetaka, Tsuda, Kazumitsu, Kanatani, Takashi, Sunouchi, Yukiko, Kaneko, Koichi, Nakayama
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Journal Title
Am. J. Physiol. Cell Physiol 291
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Local regulation of skin blood flow during cooling involving presynaptic P2 purinoceptors in rats2006
Author(s)
Tadachika, Koganezawa, Tomohisa, Ishikawa, Yukiyoshi, Fujita, Tomonari, Yamashita, Takako, Tajima, Masaki, Honda, Koichi, Nakayama
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Journal Title
Br. J. Pharmacol 148
Pages: 579-586
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Passive stretching produces Akt- and MAPK-dependent augmentations of GLUT4 translocation and glucose uptake in skeletal muscles of mice2006
Author(s)
Yoshihiko, Ito, Kazuo, Obara, Rikuko, Ikeda, Megumi, Ishii, Yoshiyuki, Tanabe, Tomohisa, Ishikawa, Koichi, Nakayama
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Journal Title
Pflugers Archiv-European Journal of Physiology 451
Pages: 803-813
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Effects of olmesartan, an AT1 receptor antagonist, on hypoxia-induced activation of ERK1/2 and pro-inflammatory signals in the mouse lung2006
Author(s)
Yoshiyuki, Tanabe, Yuki, Morikawa, Takao, Kato, Satoshi, Kanai, Taichi, Watakabe, Ami, Nishijima, Hijiri, Iwata, Kaori, Isobe, Mayumi, Ishizaki, Koichi, Nakayama
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Journal Title
Naunyn-Schmiedeberg's Arch. Pharmacol 374
Pages: 235-248
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Involvements of Rho-kinase and protein kinase C in stretch-induced triphosphorylation of myosin light chain in canine basilar artery2007
Author(s)
Kazuo, Obara, Yoshihiko, Ito, Hiroki, Shimada, Koichi, Nakayama, Tomohisa, Ishikawa
Organizer
The 80th Annual Meeting of The Japanese Pharmacological Society
Place of Presentation
Nagoya, Japan
Year and Date
2007-03-15
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Passive stretching produces Akt- and MAPK-dependent augmentations of GLUT4 translocation and glucose uptake in skeletal muscles of mice : A novel pharmacological strategy for controlling glucose metabolism2006
Author(s)
Yoshihiko, Ito, Kazuo, Obara, Rikuko, Ikeda, Megumi, Ishii, Yoshiyuki, Tanabe, Tomohisa, Ishikawa, Koichi, Nakayama
Organizer
The 79th Annual Meeting of The Japanese Pharmacological Society
Place of Presentation
Yokohama, Japan
Year and Date
2006-03-10
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Effect of olmesartan, an ATI receptor antagonist, on hypobaric hypoxia-induced activation of ERK1/2 and expression of IL-6 in mouse lung2006
Author(s)
Tomoaki, Kitayama, Yoshiyuki, Tanabe, Takao, Kato, Yuki, Morikawa, Hijiri, Iwata, Kaori, Isobe, Koichi, Nakayama
Organizer
The 79th Annual Meeting of The Japanese Pharmacological Society
Place of Presentation
Yokohama
Year and Date
2006-03-09
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Multiple phosphorylation of myosin light chain induced by hemodynamic stimulus and intracellular signaling2006
Author(s)
Koichi, Nakayama, Tomohisa, Ishikawa, Kazuo, Obara, Yoshiyuki, Tanabe, Shigeru, Nishizawa, Masakuni, Degawa
Organizer
2005US Forum, University of Shizuoka
Place of Presentation
Shizuoka Japan
Year and Date
2006-03-02
Description
「研究成果報告書概要(欧文)」より
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