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Selenoprotein P-neutralizing antibodies improve insulin secretion and glucose sensitivity in type 2 diabetes mouse models

Author

Listed:
  • Yuichiro Mita

    (Doshisha University
    Doshisha University)

  • Kaho Nakayama

    (Doshisha University)

  • Shogo Inari

    (Doshisha University)

  • Yukina Nishito

    (Doshisha University)

  • Yuya Yoshioka

    (Doshisha University)

  • Naoko Sakai

    (Doshisha University)

  • Kanade Sotani

    (Doshisha University)

  • Takahiro Nagamura

    (Doshisha University)

  • Yuki Kuzuhara

    (Doshisha University,)

  • Kumi Inagaki

    (Doshisha University)

  • Miki Iwasaki

    (Doshisha University)

  • Hirofumi Misu

    (Kanazawa University Graduate School of Medical Sciences)

  • Masaya Ikegawa

    (Doshisha University,)

  • Toshinari Takamura

    (Kanazawa University Graduate School of Medical Sciences)

  • Noriko Noguchi

    (Doshisha University)

  • Yoshiro Saito

    (Doshisha University)

Abstract

Selenoprotein P (SeP) functions as a selenium (Se)-supply protein. SeP is identified as a hepatokine, promoting insulin resistance in type 2 diabetes. Thus, the suppression of Se-supply activity of SeP might improve glucose metabolism. Here, we develop an anti-human SeP monoclonal antibody AE2 as with neutralizing activity against SeP. Administration of AE2 to mice significantly improves glucose intolerance and insulin resistance that are induced by human SeP administration. Furthermore, excess SeP administration significantly decreases pancreas insulin levels and high glucose-induced insulin secretion, which are improved by AE2 administration. Epitope mapping reveals that AE2 recognizes a region of human SeP adjacent to the first histidine-rich region (FHR). A polyclonal antibody against the mouse SeP FHR improves glucose intolerance and insulin secretion in a mouse model of diabetes. This report describes a novel molecular strategy for the development of type 2 diabetes therapeutics targeting SeP.

Suggested Citation

  • Yuichiro Mita & Kaho Nakayama & Shogo Inari & Yukina Nishito & Yuya Yoshioka & Naoko Sakai & Kanade Sotani & Takahiro Nagamura & Yuki Kuzuhara & Kumi Inagaki & Miki Iwasaki & Hirofumi Misu & Masaya Ik, 2017. "Selenoprotein P-neutralizing antibodies improve insulin secretion and glucose sensitivity in type 2 diabetes mouse models," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01863-z
    DOI: 10.1038/s41467-017-01863-z
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