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

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  • Byung Geun Ha
    Department of Nutriproteomics Graduate School of Medicine, The University of Tokyo Bunkyo‐Ku Tokyo Japan
  • Takayuki Yonezawa
    Department of Nutriproteomics Graduate School of Medicine, The University of Tokyo Bunkyo‐Ku Tokyo Japan
  • Myoung Jin Son
    Department of Applied Biological Chemistry Tokyo University of Agriculture and Technology Fuchu Tokyo Japan
  • Je Tae Woo
    Department of Nutriproteomics Graduate School of Medicine, The University of Tokyo Bunkyo‐Ku Tokyo Japan
  • Shinsuke Ohba
    Department of Bioengineering Graduate School of Engineering, The University of Tokyo Bunkyo‐Ku Tokyo Japan
  • Ung‐Il Chung
    Department of Bioengineering Graduate School of Engineering, The University of Tokyo Bunkyo‐Ku Tokyo Japan
  • Kazumi Yagasaki
    Department of Nutriproteomics Graduate School of Medicine, The University of Tokyo Bunkyo‐Ku Tokyo Japan

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<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>in vivo</jats:italic> study, nepodin suppressed the increases in fasting blood glucose levels and improved the glucose intolerance of C57BL/KsJ‐<jats:italic>db/db</jats:italic> mice, a type 2 diabetic animal model. Nepodin rescued the impaired phosphorylation of AMPK in the skeletal muscle of <jats:italic>db/db</jats:italic> 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</jats:p>

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  • BioFactors

    BioFactors 40 (4), 436-447, 2014-04-23

    Wiley

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