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Establishment of quantification method of glucagon-related peptides and elucidation of pathophysiological role of the peptides

Research Project

Project/Area Number 17K09831
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionKobe University

Principal Investigator

Minami Kohtaro  神戸大学, 医学研究科, 客員准教授 (80334176)

Co-Investigator(Kenkyū-buntansha) 横井 伯英  神戸大学, 医学研究科, 医学研究員 (70311610)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsペプチドホルモン / グルカゴン / 質量分析計 / 固相抽出法 / 糖尿病 / 免疫沈降法
Outline of Final Research Achievements

Peptide hormones exert various physiological roles and dysfunction of their secretion and action closely relate with the onset and pathophysiology of various diseases. Therefore, precise quantification of peptide hormones is essential for the disease diagnosis, pathophysiological evaluation, and assessment of therapeutic effect. In this study, we established an extraction method for glucagon and glucagon-related peptides from plasma samples, and also developed a quantification method by using mass spectrometry. We further confirm the usefulness of the method by using blood samples from animal models of obesity and diabetes and humans.

Academic Significance and Societal Importance of the Research Achievements

本研究において確立されたペプチドホルモンの測定法は、従来の免疫学的な測定法では回避することが困難である抗体の交差性の問題が解消できること、複雑なプロセッシングを受けるホルモンでも高精度な測定が可能であることなど、これまでの測定法と比較して優位性かつ独創性が高いものであり、微量な生体ペプチドを定量性・特異性を担保し迅速・効率的に測定する普遍的な方法の確立に直結する。また、本測定法により新規グルカゴン関連ペプチドの病態生理学的意義が解明されれば、糖尿病などの糖代謝疾患の病態解明に大きく寄与し、その新規診断法確立の基盤となることが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (12 results)

All 2020 2019 2018 2017 Other

All Journal Article (7 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 7 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Invited: 1 results) Remarks (1 results)

  • [Journal Article] GCN2 regulates pancreatic β-cell mass by sensing intracellular amino acid levels.2020

    • Author(s)
      Kanno A, Asahara SI, Furubayashi A, Masuda K, Yoshitomi R, Suzuki E, Takai T, Kimura-Koyanagi M, Matsuda T, Bartolome A, Hirota Y, Yokoi N, Inaba Y, Inoue H, Matsumoto M, Inoue K, Abe T, Wei FY, Tomizawa K, Ogawa W, Seino S, Kasuga M, Kido Y.
    • Journal Title

      JCI Insight.

      Volume: 5 Issue: 9 Pages: 128820-128820

    • DOI

      10.1172/jci.insight.128820

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Tumor-like features of gene expression and metabolic profiles in enlarged pancreatic islets are associated with impaired incretin-induced insulin secretion in obese diabetes: a study of ZFDM rat.2020

    • Author(s)
      Hayami T, Yokoi N, Yamaguchi T, Honda K, Murao N, Takahashi H, Wang S, Seino Y, Kamiya H, Yabe D, Sweet IR, Mizoguchi A, Nakamura J, Seino S
    • Journal Title

      J Diabetes Investig

      Volume: - Issue: 6 Pages: 1434-1447

    • DOI

      10.1111/jdi.13272

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Arsenic modifies serotonin metabolism through glucuronidation in pancreatic β-cells2019

    • Author(s)
      Carmean Christopher M.、Yokoi Norihide、Takahashi Harumi、Oduori Okechi S.、Kang Christie、Kanagawa Akiko、Kirkley Andrew G.、Han Guirong、Landeche Michael、Hidaka Shihomi、Katoh Miki、Sargis Robert M.、Seino Susumu
    • Journal Title

      American Journal of Physiology-Endocrinology and Metabolism

      Volume: 316 Issue: 3 Pages: E464-E474

    • DOI

      10.1152/ajpendo.00302.2018

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inhibition of SNAT5 Induces Incretin-Responsive State From Incretin-Unresponsive State in Pancreatic β-Cells: Study of β-Cell Spheroid Clusters as a Model2018

    • Author(s)
      Hashim Mahira、Yokoi Norihide、Takahashi Harumi、Gheni Ghupurjan、Okechi Oduori S.、Hayami Tomohide、Murao Naoya、Hidaka Shihomi、Minami Kohtaro、Mizoguchi Akira、Seino Susumu
    • Journal Title

      Diabetes

      Volume: 67 Issue: 9 Pages: 1795-1806

    • DOI

      10.2337/db17-1486

    • NAID

      40022150466

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characteristics of repaglinide effects on insulin secretion.2018

    • Author(s)
      Takahashi H, Hidaka S, Seki C, Yokoi N, Seino S.
    • Journal Title

      Eur J Pharmacol.

      Volume: 828 Pages: 52-59

    • DOI

      10.1016/j.ejphar.2018.03.025

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Essential roles of aspartate aminotransferase 1 and vesicular glutamate transporters in β-cell glutamate signaling for incretin-induced insulin secretion.2017

    • Author(s)
      Murao N, Yokoi N, Honda K, Han G, Hayami T, Gheni G, Takahashi H, Minami K, Seino S.
    • Journal Title

      PLoS One.

      Volume: 12 Issue: 11 Pages: e0187213-e0187213

    • DOI

      10.1371/journal.pone.0187213

    • NAID

      120006373802

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] β-cell signaling and insulin secretagogues: a path for improved diabetes therapy2017

    • Author(s)
      Seino S, Sugawara K, Yokoi N, Takahashi H
    • Journal Title

      Diabetes Obes Metab

      Volume: 印刷中 Issue: S1 Pages: 22-29

    • DOI

      10.1111/dom.12995

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] GLP-1 receptor agonists and DPP-4 inhibitors both normalize diabetes caused by deletion of β-cell KATP channels in mice2018

    • Author(s)
      Oduori S. Okechi, Kenju Shimomura, Harumi Takahashi, Norihide Yokoi, Kohtaro Minami, Yuko Maejima, and Susumu Seino
    • Organizer
      第61回日本糖尿病学会年次学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Incretin and beta-cell metabolic signaling2017

    • Author(s)
      横井伯英、村尾直哉、高橋晴美、清野 進
    • Organizer
      第59回日本糖尿病学会年次学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 膵β細胞グルタミン酸シグナルのインスリン分泌における役割の解明 -CRISPR/Cas9による遺伝子改変 膵β細胞株を用いた検討2017

    • Author(s)
      村尾直哉、横井伯英、韓 桂栄、グプルジャン ゲニ、清野 進
    • Organizer
      第59回日本糖尿病学会年次学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] インクレチン応答性インスリン分泌増強機構の解明:インスリン顆粒内グルタミン酸の役割2017

    • Author(s)
      グプルジャン ゲニ、横井伯英、波多野直哉、韓 桂栄、高橋晴美、清野 進
    • Organizer
      第59回日本糖尿病学会年次学術集会
    • Related Report
      2017 Research-status Report
  • [Remarks] 神戸大学大学院医学研究科分子代謝医学部門ホームページ

    • URL

      http://www.med.kobe-u.ac.jp/phys1/index.html

    • Related Report
      2018 Research-status Report 2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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