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Mechanism of energy homeostasis through organ crosstalk of glutamine metabolism

Research Project

Project/Area Number 17K09875
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Suzuki Sawako  千葉大学, 医学部附属病院, 助教 (60400892)

Co-Investigator(Kenkyū-buntansha) 田中 知明  千葉大学, 大学院医学研究院, 教授 (50447299)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords細胞内代謝 / グルタミン代謝 / 行動異常 / 糖尿病 / 肥満 / エネルギー代謝
Outline of Final Research Achievements

We demonstrated that GLS2, which is a master regulator of glutamine metabolism, was associated with metabolic syndrome and cancer. However, its detailed molecular mechanism and organ crosstalk have not been clarified. In this study, we evaluated energy intake and consumption balance and analyzed behavioral abnormalities in Gls2 knockout mice. As a result, the food intake during the day time and the amount of exercise was significantly increased in Gls2 knockout mice compared to wild-type mice. Furthermore, we revealed that pancreatic β-cell specific Gls2 knockout mice exhibited significant diabetes mellitus under high-fat diet through insulin and glucagon disorganization.

Academic Significance and Societal Importance of the Research Achievements

グルタミン代謝は糖代謝・脂質代謝・アミノ酸代謝とクロストークする重要な細胞内経路である。癌細胞においては糖代謝と並んで著明に亢進することが広く知られており我々も癌との関連で研究を進めてきたが、代謝病態における役割は不明な点が多かった。本研究の結果によりGLS2を介したグルタミン代謝の破綻は高脂肪食負荷で肥満や糖尿病を発症することを明らかとし、その機序として行動異常・摂食異常、そして膵臓におけるインスリン・グルカゴン分泌異常が関与していることを見出した。これら結果は癌と生活習慣病の共通分子基盤の解明に大きく貢献すると考えられる。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (38 results)

All 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (4 results) Journal Article (12 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 12 results,  Open Access: 12 results) Presentation (13 results) (of which Int'l Joint Research: 1 results,  Invited: 5 results) Book (6 results) Remarks (3 results)

  • [Int'l Joint Research] コロンビア大学 (Biological Science)(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] コロンビア大学 (Biological Science)(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] コロンビア大学 (Biological Science)(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Columbia University/Biological Science/Carol Prives(米国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Association of urinary free cortisol with bone formation in patients with mild autonomous cortisol secretion2021

    • Author(s)
      Ishida A, Igarashi K, Ruike Y, Ishiwata K, Naito K, Kono S, Deguchi H, Fujimoto M, Shiga A, Suzuki S, Yoshida T, Tanaka T, Tatsuno I, Yokote K, Koide H.
    • Journal Title

      Clin Endocrinol (Oxf).

      Volume: 94 Issue: 4 Pages: 544-550

    • DOI

      10.1111/cen.14385

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fracture risk assessment tool may not indicate bone fragility in women with type 2 diabetes.2020

    • Author(s)
      Ohira M, Suzuki S, Yoshida T, Koide H, Tanaka T, Tatsuno I.
    • Journal Title

      Am J Med Sci.

      Volume: S0002-9629 Issue: 5 Pages: 30119-1

    • DOI

      10.1016/j.amjms.2020.04.002

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Steroid metabolites for diagnosing and predicting clinicopathological features in cortisol-producing adrenocortical carcinoma2020

    • Author(s)
      Suzuki Sawako、Minamidate Tomoki、Shiga Akina、Ruike Yutarou、Ishiwata Kazuki、Naito Kumiko、Ishida Akiko、Deguchi Hanna、Fujimoto Masanori、Koide Hisashi、Tatsuno Ichiro、Ikeda Jun-ichiro、Yamazaki Yuto、Sasano Hironobu、Yokote Koutaro
    • Journal Title

      BMC Endocrine Disorders

      Volume: 20 Issue: 1 Pages: 1-9

    • DOI

      10.1186/s12902-020-00652-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aldosterone reduction rate after saline infusion test may be a novel prediction in patients with primary aldosteronism.2019

    • Author(s)
      27.Nagano H, Kono T, Saiga A, Kubota Y, Fujimoto M, Felizola S, Ishiwata K, Tamura A, Higuchi S, Sakuma I, Hashimoto N, Suzuki S, Koide H, Takeshita N, Sakamoto S, Ban T, Yokote K, Nakamura Y, Ichikawa T, Uno T, Tanaka T.
    • Journal Title

      J Clin Endocrinol Metab.

      Volume: 19 Issue: 3 Pages: 319-327

    • DOI

      10.1210/clinem/dgz092

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fatty acid desaturase 2 is up-regulated by the treatment with statin through geranylgeranyl pyrophosphate-dependent Rho kinase pathway in HepG2 cells2019

    • Author(s)
      26.Tanaka S, Ishihara N, Suzuki S, Watanabe Y, Nagayama D, Yamaguchi T, Ohira M, Saiki A, Tanaka T, Tatsuno I.
    • Journal Title

      Sci Rep.

      Volume: 10 Issue: 1 Pages: 10009-10009

    • DOI

      10.1038/s41598-019-46461-9

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] p53-inducible DPYSL4 associates with mitochondrial supercomplexes and regulates energy metabolism in adipocytes and cancer cells.2018

    • Author(s)
      Nagano H, Hashimoto N, Nakayama A, Suzuki S, Miyabayashi Y, Yamato A, Higuchi S, Fujimoto M, Sakuma I, Beppu M, Yokoyama M, Suzuki Y, Sugano S, Ikeda K, Tatsuno I, Manabe I, Yokote K, Inoue S, Tanaka T.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 115 Issue: 33 Pages: 8370-8375

    • DOI

      10.1073/pnas.1804243115

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Glucagonoma with necrolytic migratory erythema: Metabolic profile and detection of biallelic inactivation of DAXX Gene2018

    • Author(s)
      ①Tamura A, Ogasawara T, Fujii Y, Kaneko H, Nakayama A, Higuchi S, Hashimoto N, Miyabayashi Y, Fujimoto M, Komai E, Kono T, Sakuma I, Nagano H, Suzuki S, Koide H, Yokote K, Iseki K, Oguma R, Matsue H, Nojima H, Sugiura K, Yoshitomi H, Ohtsuka M, Rahmutulla B, Kaneda A, Inoshita N, Ogawa S, Tanaka T.
    • Journal Title

      J Clin Endocrinol Metab.

      Volume: 103 Issue: 7 Pages: 2417

    • DOI

      10.1210/jc.2017-02646

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fracture risk assessment tool (FRAX) and for the diagnosis of osteoporosis in Japanese middle-aged and elderly women: Chiba bone survey2018

    • Author(s)
      Oka R, Ohira M, Suzuki S, Yoshida T, Koide H, Tanaka T, Tatsuno I.
    • Journal Title

      Endocrine Journal

      Volume: 65 Issue: 2 Pages: 193-202

    • DOI

      10.1507/endocrj.EJ17-0331

    • NAID

      130006402991

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prednisolone-responsive Postpartum IgG4-related Hypophysitis2018

    • Author(s)
      Koide H, Shiga A, Komai E, Yamato A, Fujimoto M, Tamura A, Kono T, Nakayama A, Takiguchi T, Higuchi S, Sakuma I, Nagano H, Hashimoto N, Suzuki S, Takeda Y, Shibuya M, Nishioka H, Yamada S, Inoshita N, Ishiwatari N, Horiguchi K, Yokote K, Tanaka T.
    • Journal Title

      Internal Medicine

      Volume: 57 Issue: 3 Pages: 367-375

    • DOI

      10.2169/internalmedicine.8446-16

    • NAID

      130006329476

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multihormonal pituitary adenoma concomitant with Pit-1 and Tpit lineage cells causing acromegaly associated with subclinical Cushing's disease: a case report.2017

    • Author(s)
      Takiguchi T, Koide H, Nagano H, Nakayama A, Fujimoto M, Tamura A, Komai E, Shiga A, Kono T, Higuchi S, Sakuma I, Hashimoto N, Suzuki S, Miyabayashi Y, Ishiwatari N, Horiguchi K, Nakatani Y, Yokote K, Tanaka T.
    • Journal Title

      BMC Endocr Disord.

      Volume: 17 Issue: 1 Pages: 54-54

    • DOI

      10.1186/s12902-017-0203-5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] SEVEN FAMILIAL DYSALBUMINEMIC HYPERTHYROXINEMIA CASES IN THREE UNRELATED JAPANESE FAMILIES AND HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY ANALYSIS OF THE THYROXINE BINDING PROFILE.2017

    • Author(s)
      Nagano H, Nakagawa Y, Ishikawa N, Watanabe H, Miyabayashi Y, Nakayama A, Fujimoto M, Komai E, Shiga A, Tamura A, Kono T, Takiguchi T, Higuchi S, Sakuma I, Hashimoto N, Suzuki S, Koide H, Yokote K, Tanaka T.
    • Journal Title

      Endocr Pract.

      Volume: 23 Issue: 11 Pages: 1325-1332

    • DOI

      10.4158/ep171964.or

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Atorvastatin increases Fads1, Fads2 and Elovl5 gene expression via the geranylgeranyl pyrophosphate-dependent Rho kinase pathway in 3T3-L1 cells.2017

    • Author(s)
      Ishihara N, Suzuki S, Tanaka S, Watanabe Y, Nagayama D, Saiki A, Tanaka T, Tatsuno I.
    • Journal Title

      Mol Med Rep.

      Volume: 16 Issue: 4 Pages: 4756-4762

    • DOI

      10.3892/mmr.2017.7141

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] グルタミン代謝の破綻はフェロトーシス依存的に肝癌を増悪させる2020

    • Author(s)
      鈴木佐和子,石渡一樹,内藤久美子,出口ハンナ,類家裕太郎,石田晶子,藤本真徳,田村愛,志賀明菜,小出尚史,田中知明,横手幸太郎
    • Organizer
      第93回日本内分泌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] CRH/GRH/TRH/LHRH四者負荷試験の代替としてのGHRP2/TRH/LHRH三者負荷試験の有用性2020

    • Author(s)
      鈴木佐和子、類家裕太郎、石渡一樹、内藤久美子、出口ハンナ、石田晶子、志賀明菜、田村愛、藤本真徳、小出尚史、横手幸太郎
    • Organizer
      第93回日本内分泌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 膵β細胞分化におけるGlutaminase 2の役割解明2020

    • Author(s)
      出口ハンナ1)、鈴木佐和子1)、田中知明2)、横手幸太郎1)
    • Organizer
      第93回日本内分泌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Glutaminolysisの糖尿病および癌における役割解明2020

    • Author(s)
      鈴木佐和子、田中知明、横手幸太郎
    • Organizer
      第58回糖尿病関東甲信越地方会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] グルタミン代謝制御遺伝子Glutaminase2が癌・老化関連疾患に及ぼす影響2019

    • Author(s)
      鈴木佐和子
    • Organizer
      第19会日本抗加齢医学会総会シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 両側副腎皮質大結節性過形成の新たな分子病態の解明2019

    • Author(s)
      鈴木佐和子
    • Organizer
      第20回日本内分泌学会関東甲信越支部学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 副腎皮質癌における新規遺伝子変異の同定と新たな細胞死Ferroptosisを介した役割2019

    • Author(s)
      志賀明菜, 鈴木佐和子, 横手幸太郎
    • Organizer
      第92回日本内分泌学会学術総会 2019年5月 (Young Investigator Award受賞)
    • Related Report
      2019 Research-status Report
  • [Presentation] グルタミン代謝を介した新たな糖代謝制御機構の解明2019

    • Author(s)
      出口ハンナ, 鈴木佐和子, 石渡一樹, 石田晶子, 田村愛, 藤本真徳, 志賀明菜, 佐久間一基, 永野秀和, 小出尚史, 田中知明, 横手幸太郎
    • Organizer
      第92回日本内分泌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 副腎癌における予後予測可能なステロイド中間代謝産物の検討2019

    • Author(s)
      南舘智樹, 鈴木佐和子, 志賀明菜, 石渡一樹, 内藤久美子, 石田晶子, 出口ハンナ, 藤本真徳, 田村愛, 佐久間一基, 田中知明, 小出尚史, 横手幸太郎
    • Organizer
      第20回日本内分泌学会関東甲信越支部学術集会 2019年9月 (会長賞受賞)
    • Related Report
      2019 Research-status Report
  • [Presentation] グルタミン代謝制御遺伝子Glutaminase2が癌・老化関連疾患に及ぼす影響2019

    • Author(s)
      鈴木佐和子、横手幸太郎
    • Organizer
      第19会日本抗加齢医学会総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 遺伝子異常からコルチゾール産生副腎腫瘍の病態に迫る2018

    • Author(s)
      鈴木佐和子
    • Organizer
      第28回臨床内分泌代謝update
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] グルタミン代謝の生活習慣病と癌における役割とその分子病態2018

    • Author(s)
      鈴木佐和子
    • Organizer
      第18回TCカンファランス
    • Related Report
      2018 Research-status Report
  • [Presentation] The roles of GLS2 in life related disease and liver cancer2017

    • Author(s)
      Sawako Suzuki
    • Organizer
      p53 conference in Columbia
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Book] 第30回臨床内分泌代謝 Update Proceeding2021

    • Author(s)
      石渡一樹、鈴木佐和子、横手幸太郎
    • Total Pages
      3
    • Publisher
      日本内分泌学会
    • Related Report
      2020 Annual Research Report
  • [Book] 内分泌Up To Date (神経内分泌腫瘍)2019

    • Author(s)
      鈴木佐和子, 横手幸太郎
    • Total Pages
      4
    • Publisher
      南江堂
    • Related Report
      2019 Research-status Report
  • [Book] 内分泌機能検査実施マニュアル 改訂第三版2019

    • Author(s)
      鈴木佐和子, 龍野一郎, 横手幸太郎
    • Total Pages
      2
    • Publisher
      診断と治療社
    • Related Report
      2019 Research-status Report
  • [Book] 内分泌機能検査実施マニュアル 改訂第3版2018

    • Author(s)
      鈴木佐和子、龍野一郎、横手幸太郎
    • Total Pages
      2
    • Publisher
      診断と治療社
    • Related Report
      2018 Research-status Report
  • [Book] 細胞 がん細胞における特異的細胞内代謝と治療抵抗性2017

    • Author(s)
      中山哲俊、鈴木佐和子、田中知明
    • Total Pages
      5
    • Publisher
      ニューサイエンス社
    • Related Report
      2017 Research-status Report
  • [Book] 内分泌性高血圧疾患診療マニュアル改訂第二版2017

    • Author(s)
      鈴木佐和子、横手幸太郎
    • Total Pages
      2
    • Publisher
      診断と治療社
    • Related Report
      2017 Research-status Report
  • [Remarks] 日本糖尿病学会 キラリ 女性医師

    • URL

      http://www.jds.or.jp/modules/education/?content_id=73

    • Related Report
      2020 Annual Research Report
  • [Remarks] グルタミン代謝の生体内における役割およびその分子メカニズム解明

    • URL

      https://www.m.chiba-u.ac.jp/dept/clin-cellbiol/research/diabetic/study_05/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 両側副腎皮質大結節性過形成 PMAHの病態解明

    • URL

      https://www.m.chiba-u.ac.jp/dept/clin-cellbiol/research/diabetic/study_04/

    • Related Report
      2020 Annual Research Report

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Published: 2017-04-28   Modified: 2022-02-21  

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