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The elucidation of roles of GSK3 on the regulation of energy metabolism for developing therapeutic strategy of T2DM

Research Project

Project/Area Number 25461357
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

TANABE Katsuya  山口大学, 医学部附属病院, 助教 (00397994)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords糖尿病 / GSK3 / 膵β細胞 / 小胞体ストレス / エネルギー代謝 / PPARγ / GSK-3 / 脂肪細胞 / アポトーシス
Outline of Final Research Achievements

We aimed to elucidate the pathophysiological roles of GSK-3 in developing type 2 diabetes. Inactivation of the GSK3 attenuated ER stress-induced β-cell apoptosis with concomitant inhibition ATF4 protein degradation. As a consequence of ATF4 modulation, GSK-3 inhibition resulted in an alteration of translational adaptation to ER stress. On the other hand, GSK3 is activated in adipose tissue of mice fed high fat diet. In addition, GSK-3 negatively regulates transcriptional activity of PPARγ by giving a direct phosphorylation, suggesting that it may play an important role in the regulation of energy metabolism. These results indicate that aberrant activation of GSK3 is implicated to both β-cell loss and a modulation of energy metabolism. Therefore, understanding the mechanisms by which GSK3 modulates glucose metabolism helps developing new strategy to the treatment of type 2 diabetes.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (19 results)

All 2015 2014 2013

All Journal Article (7 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (10 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results) Book (2 results)

  • [Journal Article] Wolfram症候群研究の現況と展望2015

    • Author(s)
      田部勝也
    • Journal Title

      日本臨床

      Volume: 73 Pages: 341-349

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 糖尿病と小胞体ストレス2015

    • Author(s)
      永尾優子 田部勝也 谷澤幸生
    • Journal Title

      最新医学

      Volume: 70 Pages: 496-503

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Wolfram syndrome: clinical features, molecular genetics of WFS1 gene.2015

    • Author(s)
      Tanabe K, Matsunaga K, Hatanaka M, Akiyama M, Tanizawa Y.
    • Journal Title

      Nihon Rinsho

      Volume: 73 Pages: 341-349

    • NAID

      40020332982

    • Related Report
      2014 Research-status Report
  • [Journal Article] 小胞体ストレスと膵β細胞死2015

    • Author(s)
      田部勝也、谷澤幸生
    • Journal Title

      日本体質医学会雑誌

      Volume: 77 Pages: 14-20

    • NAID

      40020373465

    • Related Report
      2014 Research-status Report
  • [Journal Article] Wolfram syndrome in the Japanese population; molecular analysis of WFS1 gene and characterization of clinical features.2014

    • Author(s)
      Matsunaga K, Tanabe K, Inoue H, Okuya S, Ohta Y, Akiyama M, Taguchi A, Kora Y, Okayama N, Yamada Y, Wada Y, Amemiya S, Sugihara S, Nakao Y, Oka Y, Tanizawa Y.
    • Journal Title

      PLOS ONE

      Volume: 9 Issue: 9 Pages: e106906-e106906

    • DOI

      10.1371/journal.pone.0106906

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Clock-controlled output gene Dbp is a regulator of Arnt/Hif-1β gene expression in pancreatic islet β-cells2013

    • Author(s)
      Nakabayashi H, Ohta Y, Yamamoto M, Susuki Y, Taguchi A, Tanabe K, Kondo M, Hatanaka M, Nagao Y, Tanizawa Y
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 434 Issue: 2 Pages: 370-5

    • DOI

      10.1016/j.bbrc.2013.03.084

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A sibling case of Wolfram syndrome with a novel mutation Y652X in WFS12013

    • Author(s)
      Iwasaki N., Fukawa K., Matsuo M., Urano M., Watanabe M., Ono Y., Tanabe K., Tanizawa Y., Ogata M., Ide R., Takizawa M., Nagata S., Osawa M., Uchigata Y., Saito K.
    • Journal Title

      Diabetology International

      Volume: 5 Issue: 2 Pages: 148-153

    • DOI

      10.1007/s13340-013-0145-8

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Wfs1欠損マウスにおける膵β細胞脱分化とその意義の解明2015

    • Author(s)
      椎木幾久子 田部勝也 谷澤幸生
    • Organizer
      第27回分子糖尿病学研究会
    • Place of Presentation
      丸ビルホール&カンファレンススクェア(東京都千代田区)
    • Year and Date
      2015-12-05
    • Related Report
      2015 Annual Research Report
  • [Presentation] Wfs1 deficiency compromises beta cell identity and results in loss of functional beta cell mass2015

    • Author(s)
      田部勝也 椎木幾久子 谷澤幸生
    • Organizer
      Keystone symposia Kyoto
    • Place of Presentation
      ウェスティン都ホテル(京都府京都市)
    • Year and Date
      2015-10-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Wfs1 deficiency compromises beta cell identity and results in loss of functional beta cell mass2015

    • Author(s)
      椎木幾久子 田部勝也 谷澤幸生
    • Organizer
      第75回米国糖尿病学会
    • Place of Presentation
      ボストンコンベンションセンター ボストン(USA)
    • Year and Date
      2015-06-05
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Wolfram症候群の実態と糖尿病発症機構の解明2015

    • Author(s)
      田部勝也
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      海峡メッセ下関(山口県・下関市)
    • Year and Date
      2015-05-21 – 2015-05-23
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Wolfram症候群の診断と発症機構の解明2015

    • Author(s)
      田部勝也
    • Organizer
      第58回糖尿病学会年次学術集会
    • Place of Presentation
      シーモール下関(山口県下関市)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Wfs1欠損膵島における膵β細胞脱分化機構の解析2015

    • Author(s)
      椎木幾久子
    • Organizer
      第58回糖尿病学会年次学術集会
    • Place of Presentation
      シーモール下関(山口県下関市)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] Gsk-3 によるIntegrated Stress Response(ISR)制御と膵β細胞アポトーシス誘導における意義とその解明2015

    • Author(s)
      永尾優子 田部勝也 谷澤幸生
    • Organizer
      第58回糖尿病学会年次学術集会
    • Place of Presentation
      シーモール下関(山口県下関市)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] Role of GSK3 in the development of beta cell failure2014

    • Author(s)
      田部勝也
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪リーガロイヤルホテル【大阪府】
    • Year and Date
      2014-05-22 – 2014-05-24
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Role of GSK3 in the development of beta cell failure2014

    • Author(s)
      田部勝也
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪リーガロイヤルホテル(大阪)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] SCFβTrCP and GSK3-mediated degradation of ATF4 is a pro-apoptotic mechanism in pancreatic beta cell under ER stress.2013

    • Author(s)
      田部勝也
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本メルパルクホール(熊本)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Book] Islet Equality2014

    • Author(s)
      田部勝也
    • Total Pages
      42
    • Publisher
      メディカルレビュー社
    • Related Report
      2013 Research-status Report
  • [Book] Diabetes Frontier2013

    • Author(s)
      田部勝也
    • Total Pages
      780
    • Publisher
      メディカルレビュー社
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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