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Diabetes-induced disturbances in energy and lipid metabolism in the brain

Research Project

Project/Area Number 25461373
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionThe University of Tokyo

Principal Investigator

Suzuki Ryo  東京大学, 医学部附属病院, 講師 (20396732)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords糖尿病 / 脳 / SCAP / 認知機能 / アストロサイト / ステロール / 脳脂質代謝 / コレステロール合成 / AMPK
Outline of Final Research Achievements

Diabetes mellitus increases risk for various CNS disorders including cognitive impairment. We focused on alterations in sterol metabolism in the brain. In diabetic mouse brains, cholesterol biosynthesis is reduced due to insufficient insulin action, accompanied by down-regulation of a sterol-sensor molecule SCAP. We found that haploinsufficiency of Scap gene in the whole brain caused impaired cognitive function. AMPK activation, mimicking a diabetic state in the brain, reduced SCAP in astroglial cells. Furthermore, induction of SCAP deficiency in astrocytes provoked disturbances in long-term memory and social cognition.

Report

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

    (23 results)

All 2016 2015 2014 2013 Other

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (16 results) (of which Invited: 9 results) Remarks (1 results)

  • [Journal Article] Association between self-stigma and self-care behaviors in patients with type 2 diabetes: A cross-sectional study2016

    • Author(s)
      Kato A, Fujimaki Y, Fujimori S, Isogawa A, Onishi Y, Suzuki R, Yamauchi T, Ueki K, Kadowaki T, Hashimoto H
    • Journal Title

      BMJ Open Diabetes Res Care

      Volume: 4 Issue: 1 Pages: 1

    • DOI

      10.1136/bmjdrc-2015-000156

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Calorie restriction-mediated restoration of hypothalamic signal transducer and activator of transcription 3 (STAT3) phosphorylation is not effective for lowering the body weight set point in IRS-2 knockout obese mice2015

    • Author(s)
      Senda S, Inoue A, Mahmood A, Suzuki R, Kamei N, Kubota N, Watanabe T, Aoyama M, Nawaz A, Ohkuma Y, Tsuneyama K, Koshimizu Y, Usui I, Saeki K, Kadowaki T and Tobe K.
    • Journal Title

      Diabetology International

      Volume: 6 Issue: 4 Pages: 321-335

    • DOI

      10.1007/s13340-015-0205-3

    • NAID

      40020684042

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential effects of angiopoietin-like 4 in brain and muscle on regulation of lipoprotein lipase activity2014

    • Author(s)
      Vienberg SG, Kleinridders A, Suzuki R, Kahn CR
    • Journal Title

      Molecular Metabolism

      Volume: 4 Issue: 2 Pages: 144-150

    • DOI

      10.1016/j.molmet.2014.11.003

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deregulation of Pancreas-Specific Oxidoreductin ERO1beta in the Pathogenesis of Diabetes Mellitus2014

    • Author(s)
      Awazawa, M. Futami, T. Sakada, M. Kaneko, K. Ohsugi, M. Nakaya, K. Terai, A. Suzuki, R. Koike, M. Uchiyama, Y. Kadowaki, T. Ueki, K.
    • Journal Title

      Mol Cell Biol

      Volume: 34 Issue: 7 Pages: 1290-1299

    • DOI

      10.1128/mcb.01647-13

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lung abscess without sepsis in a patient with diabetes with refractory episodes of spontaneous hypoglycemia: a case report and review of the literature.2014

    • Author(s)
      Toda G, Fujishiro M, Yamada T, Shojima N, Sakoda H, Suzuki R, Yamauchi T, Ueki K, Kadowaki T.
    • Journal Title

      J Med Case Rep

      Volume: 8 Issue: 1 Pages: 51-51

    • DOI

      10.1186/1752-1947-8-51

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Maratos-Flier E, Kahn CR. Reduction of thecholesterol sensor SCAP in the brains of mice causes impaired synaptic transmission and altered cognitive function.2013

    • Author(s)
      Suzuki R*, Ferris HA*, Chee MJ
    • Journal Title

      PLoS Biol

      Volume: 11 Issue: 4 Pages: e1001532-e1001532

    • DOI

      10.1371/journal.pbio.1001532

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 糖尿病に合併する認知症の予防2016

    • Author(s)
      鈴木亮
    • Organizer
      第50回糖尿病学の進歩
    • Place of Presentation
      東京
    • Year and Date
      2016-02-19
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 糖尿病と認知症2015

    • Author(s)
      鈴木亮
    • Organizer
      第30回日本糖尿病合併症学会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-11-27
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 糖尿病が脳に与える影響2015

    • Author(s)
      鈴木亮
    • Organizer
      第30回日本糖尿病合併症学会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-11-27
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 脳グリア細胞におけるAMPK活性化は 複数の機序を介してステロールセンサー 分子SCAPを減少させる2015

    • Author(s)
      渡辺隆介、鈴木亮、亀井望、齋木邦子、周聖浦、寺井愛、門脇孝
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] マウス脳アストロサイトにおけるSREBPシャペロン蛋白SCAPの役割2015

    • Author(s)
      周聖浦、鈴木亮、渡辺隆介、齋木邦子、寺井愛、亀井望、門脇孝
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 糖尿病における認知症の発症機序と病態2015

    • Author(s)
      鈴木亮、 門脇孝
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 糖尿病における認知症の発症機序と病態2015

    • Author(s)
      鈴木亮、門脇孝
    • Organizer
      第49回糖尿病学の進歩
    • Place of Presentation
      ラヴィール岡山(岡山)
    • Year and Date
      2015-02-20
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 糖尿病と中枢神経系・認知症2014

    • Author(s)
      鈴木亮、門脇孝
    • Organizer
      第29回日本糖尿病合併症学会
    • Place of Presentation
      都市センターホテル(東京)
    • Year and Date
      2014-10-04
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 脳グリア細胞におけるAMPK活性化は複数の機序を介してステロールセンサー分子SCAPを減少させる2014

    • Author(s)
      渡辺隆介、鈴木亮、亀井望、齋木邦子、周聖浦、寺井愛、原口美貴子、門脇孝
    • Organizer
      第29回日本糖尿病合併症学会
    • Place of Presentation
      都市センターホテル(東京)
    • Year and Date
      2014-10-04
    • Related Report
      2014 Research-status Report
  • [Presentation] 脳グリア細胞におけるAMPK活性化刺激は複数の機序を介してステロールセンサー分子SCAPを減少させる2014

    • Author(s)
      鈴木亮、渡辺隆介、亀井望、齋木邦子、周聖浦、寺井愛、原口美貴子、門脇孝
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      リーガロイヤルホテル(大阪)
    • Year and Date
      2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] 脳の脂質代謝と糖尿病2014

    • Author(s)
      鈴木亮
    • Organizer
      第87回日本内分泌学会学術総会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Year and Date
      2014-04-25
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 脳アストロサイトのAMPK活性化はステロールセンサー分子SCAPを減少させる2013

    • Author(s)
      鈴木亮、亀井望、齋木邦子、寺井愛、原口美貴子、C. Ronald Kahn、門脇孝
    • Organizer
      第86回日本内分泌学会学術総会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] 脳アストロサイトのAMPK活性化はステロールセンサー分子SCAPを減少させる2013

    • Author(s)
      鈴木亮、亀井望、齋木邦子、寺井愛、原口美貴子、C. Ronald Kahn、門脇孝
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] 糖尿病治療薬と発癌リスク2013

    • Author(s)
      鈴木亮
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 脳アストロサイトのAMPK活性化はステロールセンサー分子SCAPを減少させる2013

    • Author(s)
      鈴木亮、亀井望、齋木邦子、渡辺隆介、寺井愛、原口美貴子、C. Ronald Kahn、門脇孝
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Expectation for Incretin: Diabetes and Cognitive Impairment2013

    • Author(s)
      Ryo Suzuki
    • Organizer
      APDO Symposium 2013
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
    • Invited
  • [Remarks] Kadowaki Lab website

    • URL

      http://dm301k.umin.jp/index.html

    • Related Report
      2015 Annual Research Report 2014 Research-status Report

URL: 

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

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