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Mitochondrial dynamics plays important roles in pancreas beta cell and hepatocytes to regulate glucose and lipid metabolism.

Research Project

Project/Area Number 23591356
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Endocrinology
Research InstitutionKyushu University

Principal Investigator

NOMURA Masatoshi  九州大学, 大学病院, 講師 (30315080)

Co-Investigator(Renkei-kenkyūsha) ISHIHARA Naotada  久留米大学, 分子生命科学, 教授 (10325516)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsミトコンドリアダイナミクス / インスリン分泌 / Drp1 / 小胞体ストレス / 脂肪肝炎 / 糖尿病 / 非アルコール性脂肪肝炎 / インスリン抵抗性 / 臓器間ネットワーク
Research Abstract

Mitochondria have essential roles in the aerobic generation of ATP by oxidative phosphorylation, as well as in variety of cellular processes such as apoptosis and Ca2+ signaling. The mitochondrial morphology changes dynamically by a balanced fusion and fission processes that occur in response to cellular energy demands, differentiation or pathogenic conditions. In order to clarify the roles of mitochondrial fission in pancreatic beta cells and hepatocytes in vivo, we used a Cre-loxP system to disrupt Drp1 in pancreatic beta cells (Drp1betaKO) and hepatocytes (Drp1LiKO), respectively. Drp1betaKO mice showed defective insulin secretion in response to glucose and overt diabetes. Upon high fat diet, Drp1LiKO mice developed non-alcoholic steatohepatitis with marked elevation of the endoplasmic reticulum stress markers.
Collectively, mitochondrial dynamics plays important roles in pancreas beta cell and hepatocytes to meet energy demand.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (28 results)

All 2014 2013 2012 2011 Other

All Journal Article (16 results) (of which Peer Reviewed: 15 results,  Open Access: 1 results) Presentation (8 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Expression of glucagon-like peptide I receptor and its effects on biological behavior in pancreatic neuroendocrine tumors2014

    • Author(s)
      Cases AI, Ohtsuka T, Fujino M, Kozono S, Zhao M, Ohuchida K, Aishima S, Nomura M, Mizumoto K, Tanaka M
    • Journal Title

      Pancreas

      Volume: 43 Issue: 1 Pages: 1-6

    • DOI

      10.1097/mpa.0b013e3182a71537

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SMAD2 disruption in meuse pancreatic beta cells leads to islet hyperplasia and impaired insulin secretion due to the attenuation of ATP-sengitive K+ channel activity.2014

    • Author(s)
      Nomura M, Zhu HL, Wang L, Morinaga H, Takayanagi R, Teramoto N.
    • Journal Title

      Diabetologia

      Volume: 57 Issue: 1 Pages: 157-166

    • DOI

      10.1007/s00125-013-3062-2

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prolyl hydroxylase domain protein 2 plays a critical role in diet-induced obesity and glucose intolerance2013

    • Author(s)
      Matsuura H, Ichiki T, Inoue E, Nomura M, Miyazaki R, Hashimoto T, Ikeda J, Takayanagi R. Fong GH, Sunagawa K.
    • Journal Title

      Circulation

      Volume: 127 Issue: 21 Pages: 2078-87

    • DOI

      10.1161/circulationaha.113.001742

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activin stimulates CYP19A gene expression in the human ovarian ovarian granulosa cell like KGN cells via the Smad2 signaling pathway.2013

    • Author(s)
      Nomura M. Sakamoto R, Morinnga H, Wang L, Mukasa C, Takayanagi R.
    • Journal Title

      Biochem Biophys Res Comun

      Volume: 436 Issue: 3 Pages: 443-448

    • DOI

      10.1016/j.bbrc.2013.05.124

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The cell polarity protein mInsc regulates neutrophil chemotaxis via a noncanonical G protein signaling pathway2013

    • Author(s)
      Kamakura S., Nomura M., Hayase J., Iwakiri Y., Nishikimi A., Fukui Y., Takayanagi R., Sumimoto H.
    • Journal Title

      Dev Cell

      Volume: 26 Issue: 3 Pages: 292-302

    • DOI

      10.1016/j.devcel.2013.06.008

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Smad2/3 and IRF4 play a cooperative role in IL-9-producing T cell induction.2013

    • Author(s)
      Tamiya T, Ichiyama K, Kotani H, Fukaya T, Sekiya T, et al.
    • Journal Title

      J Immunol.

      Volume: 191 Issue: 5 Pages: 2360-2371

    • DOI

      10.4049/jimmunol.1301276

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles for corticotropin-releasing factor receptor type 1 in energy homeostasis in mice.2013

    • Author(s)
      Sakamoto R. Matsubara E, Nomura M, Wang L, Kawahara Y, Yanase T, Nawata H, Takayanngi R.
    • Journal Title

      Metabolism

      Volume: 62 Issue: 12 Pages: 1739-1748

    • DOI

      10.1016/j.metabol.2013.08.005

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activin type IB receptor signaling in prostate cancer cells promotes lymph node metastasis in a xenograft model.2013

    • Author(s)
      Nomura M, Tanaka K, Wang L, Goto Y, Mukasa C, Morinaga H, Takayanagi R
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 430 Issue: 1 Pages: 340-346

    • DOI

      10.1016/j.bbrc.2012.11.011

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Smad2 and Smad3 are redundantly essential for the suppression of iNOS synthesis in macrophages by regulating IRF3 and STAT1 pathways2012

    • Author(s)
      Sugiyama Yuki, 他
    • Journal Title

      International Immunology

      Volume: 24 Issue: 4 Pages: 253-256

    • DOI

      10.1093/intimm/dxr126

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Perilipin 5, a lipid droplet-binding protein, protects the heart from oxidative damage by preventing excess fatty acid oxidation2012

    • Author(s)
      Kuramoto K, Okamura T, Yamaguchi T, Nakamura TY, et.al.
    • Journal Title

      J. Biol. Chem.

      Volume: 287 Issue: 28 Pages: 23852-63

    • DOI

      10.1074/jbc.m111.328708

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] ミトコンドリアダイナミクスによるエネルギー代謝調節機構の解明2012

    • Author(s)
      野村政壽
    • Journal Title

      Therapeutic Research

      Volume: 33 Pages: 829-833

    • Related Report
      2012 Research-status Report
  • [Journal Article] p32/gC1qR is indispensable for fetal development and mitochondrial translation: importance of its RNA binding ability.2012

    • Author(s)
      Yagi M, Uchiumi T, Takazaki S, Okuno B, Nomura M, Yoshida S, Kanki T, Kang D
    • Journal Title

      Nuc Acid Res

      Volume: 19 Issue: 19 Pages: 9717-37

    • DOI

      10.1093/nar/gks774

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reduced arterial sitiffness in patients with acromegaly: non-invasive assessment by the cardio-ankle vascular index (CAVI)2012

    • Author(s)
      Matsuda Y, Kawate H, Matsuzaki C, Sakamoto R, Abe I, Shibue K, Kohno M, Adachi M, Ohnaka K, Nomura M, Takayanagi R
    • Journal Title

      Endocrine Journal

      Volume: 60 Pages: 29-36

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Smad2 disruption in the central nervous system leads to aberrant cerebellar development and early postnatal ataxia in mice2011

    • Author(s)
      Wang L, Nomura M, Goto Y, Tanaka K, Sakamoto R, Abe I, Sakamoto S, Shibata A, Enciso PL, Adachi M, Ohnaka K, Kawate H, Takayanagi R
    • Journal Title

      Journal of Biological Chemistry

      Volume: 286 Pages: 18766-18774

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] miR126 positively regulates mast cell proliferation and cytokine production through suppressing Spred12011

    • Author(s)
      Ishizaki T, Tamiya T, Taniguchi K, Morita R, Kato R, Okamoto F, Saeki K, Nomura M, Nojima Y, Yoshimura A
    • Journal Title

      Genes to Cells

      Volume: 16 Pages: 803-814

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] H3K9 methyltransferase recruitment to the IL-2 promoter is a mechanism of suppression of IL-2 transcription by the TGF-β-Smad pathway2011

    • Author(s)
      Wakabayashi Y, Tamiya T, Takeda I, Fukaya T, Sugiyama Y, Inoue N, Kimura A, Morita R, Kashiwagi I, Takimoto T, Nomura M, Yoshimura A
    • Journal Title

      Journal of Biological Chemistry

      Volume: 286 Pages: 35456-35465

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 遺伝子改変マウスを用いた消化管味覚生理研究の最前線2014

    • Author(s)
      野村政壽
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      水前寺青年会館ホール
    • Related Report
      2013 Annual Research Report
  • [Presentation] A mammalian homolog of Inscuteable involves in the regulation of energy homeostasis in mice.2013

    • Author(s)
      Noguchi Y, Nomura M, Kamakura S, Sumimoto H, Takayanagi R
    • Organizer
      84th The Endocrine Society’s annual meeting
    • Place of Presentation
      San Francisco Moscone Center
    • Related Report
      2013 Annual Research Report
  • [Presentation] Mitochondrial dynamics in energy homeostasis2013

    • Author(s)
      Nomura M
    • Organizer
      35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society
    • Place of Presentation
      Osaka International Convention Center
    • Related Report
      2013 Annual Research Report
  • [Presentation] Role of Drp-1 in pancreas β cells2011

    • Author(s)
      Masatoshi Nomura
    • Organizer
      Mitochondrial Dynamics: from mechanism to disease
    • Place of Presentation
      Sardinia, Italy
    • Related Report
      2011 Research-status Report
  • [Presentation] Modulation of Androgen Receptor function by Sonic Hedgehog Signaling in Prostate Cancer2011

    • Author(s)
      Masatoshi Nomura
    • Organizer
      The 42nd International Symposium of The Princess Takamatsu Cancer Research Fund(招待講演)
    • Place of Presentation
      Hotel Grand Palace, Tokyo, Japan
    • Related Report
      2011 Research-status Report
  • [Presentation] 遺伝子改変マウスを用いた生活習慣病研究

    • Author(s)
      野村政壽
    • Organizer
      第85回日本生化学会
    • Place of Presentation
      福岡国際会議場
    • Related Report
      2012 Research-status Report
  • [Presentation] 進行前立腺癌における去勢抵抗性獲得の分子機構

    • Author(s)
      野村政壽
    • Organizer
      第30回日本アンドロロジー学会学術大会(招待講演)
    • Place of Presentation
      東京都:都市センターホテル
    • Related Report
      2011 Research-status Report
  • [Presentation] ミトコンドリアダイナミクスと糖代謝調節

    • Author(s)
      野村政壽
    • Organizer
      第84回日本生化学会大会:シンポジウム
    • Place of Presentation
      国立京都国際会館
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://www.med.kyushu-u.ac.jp/intmed3/general_1.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 九州大学大学院医学研究院 病態制御内科学

    • URL

      http://www.med.kyushu-u.ac.jp/intmed3/general_1.html

    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.med.kyushu-u.ac.jp/intmed3/general_1.html

    • Related Report
      2011 Research-status Report
  • [Patent(Industrial Property Rights)] Drp1欠損非ヒト哺乳動物2013

    • Inventor(s)
      三原勝芳、石原直忠、野村政壽
    • Industrial Property Rights Holder
      株式会社ジェンテック
    • Acquisition Date
      2013-07-05
    • Related Report
      2013 Final Research Report
    • Overseas

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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