Mechanism of energy homeostasis through organ crosstalk of glutamine metabolism
Project/Area Number |
17K09875
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Endocrinology
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Research Institution | Chiba University |
Principal Investigator |
Suzuki Sawako 千葉大学, 医学部附属病院, 助教 (60400892)
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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)
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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)
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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.
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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。
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Report
(5 results)
Research Products
(38 results)
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[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.
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Journal Title
Clin Endocrinol (Oxf).
Volume: 94
Issue: 4
Pages: 544-550
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
J Clin Endocrinol Metab.
Volume: 19
Issue: 3
Pages: 319-327
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Proc Natl Acad Sci U S A.
Volume: 115
Issue: 33
Pages: 8370-8375
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Glucagonoma with necrolytic migratory erythema: metabolic profile and detection of biallelic inactivation of DAXX gene.2018
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.
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Journal Title
J Clin Endocrinol Metab.
Volume: 23
Issue: 7
Pages: 1-4
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Internal Medicine
Volume: 57
Issue: 3
Pages: 367-375
DOI
NAID
ISSN
0918-2918, 1349-7235
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
BMC Endocr Disord.
Volume: 17
Issue: 1
Pages: 54-54
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Endocr Pract.
Volume: 23
Issue: 11
Pages: 1325-1332
DOI
Related Report
Peer Reviewed / Open Access
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[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
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[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
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[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
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