Antidiabetic effect of nepodin, a component of Rumex roots, and its modes of action in vitro and in vivo

Authors

  • Byung Geun Ha,

    1. Department of Nutriproteomics, Graduate School of Medicine, The University of Tokyo, Bunkyo-Ku, Tokyo, Japan
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  • Takayuki Yonezawa,

    1. Department of Nutriproteomics, Graduate School of Medicine, The University of Tokyo, Bunkyo-Ku, Tokyo, Japan
    2. Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Bunkyo-Ku, Tokyo, Japan
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  • Myoung Jin Son,

    1. Department of Applied Biological Chemistry, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan
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  • Je Tae Woo,

    1. Department of Nutriproteomics, Graduate School of Medicine, The University of Tokyo, Bunkyo-Ku, Tokyo, Japan
    2. Department of Research and Development, Erina Co., Inc., Minato-Ku, Tokyo, Japan
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  • Shinsuke Ohba,

    1. Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Bunkyo-Ku, Tokyo, Japan
    2. Center for Disease Biology and Integrative Medicine, The University of Tokyo, Bunkyo-Ku, Tokyo, Japan
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  • Ung-Il Chung,

    1. Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Bunkyo-Ku, Tokyo, Japan
    2. Center for Disease Biology and Integrative Medicine, The University of Tokyo, Bunkyo-Ku, Tokyo, Japan
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  • Kazumi Yagasaki

    Corresponding author
    1. Department of Nutriproteomics, Graduate School of Medicine, The University of Tokyo, Bunkyo-Ku, Tokyo, Japan
    2. Department of Applied Biological Chemistry, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan
    • Address for correspondence: Kazumi Yagasaki, PhD, Department of Applied Biological Chemistry, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183–8509, Japan. Tel./Fax: +81-42-367–5714; E-mail: yagasaki@cc.tuat.ac.jp.

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Abstract

Many active components derived from edible natural resources such as plant extracts have recently attracted attention for their potential use as functional foods or drugs for preventing and treating metabolic diseases such as diabetes. To obtain a novel modulator of glucose metabolism, we conducted screening of a small compound library in cultured L6 myotubes. We identified nepodin that stimulated glucose uptake dose-dependently in differentiated L6 myotubes. The stimulatory effect of nepodin on glucose uptake was abrogated by a 5′-adenosine monophosphate-activated protein kinase (AMPK) inhibitor. In addition, nepodin stimulated the phosphorylation of AMPK. Nepodin also stimulated the translocation of GLUT4 to the plasma membrane in L6 myoblasts transfected with a Glut4 cDNA-coding vector and in differentiated L6 myotubes. In in vivo study, nepodin suppressed the increases in fasting blood glucose levels and improved the glucose intolerance of C57BL/KsJ-db/db mice, a type 2 diabetic animal model. Nepodin rescued the impaired phosphorylation of AMPK in the skeletal muscle of db/db mice. These results suggest that nepodin has an antidiabetic effect, which is at least partly mediated by stimulation of GLUT4 translocation via AMPK activation by nepodin. © 2014 BioFactors, 40(4):436–447, 2014

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