New developments in basic and applied adiponectin research toward reduction of dementia risk and realization of healthy longevity
| Project/Area Number |
19H01052
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
岩部 美紀 東京大学, 医学部附属病院, 特任准教授 (70392529)
岩部 真人 東京大学, 医学部附属病院, 准教授 (30557236)
山内 敏正 東京大学, 医学部附属病院, 教授 (40372370)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥45,890,000 (Direct Cost: ¥35,300,000、Indirect Cost: ¥10,590,000)
Fiscal Year 2021: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2020: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2019: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
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| Keywords | アディポネクチン / アディポネクチン受容体 / 健康長寿 / 認知症 / 糖尿病合併症 |
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| Outline of Research at the Start |
アディポネクチン及びその受容体（AdipoR）の作用が肥満に伴い低下することにより、メタボリックシンドローム・2型糖尿病・動脈硬化症が引き起こされる。本課題では、AdipoRの新規シグナル伝達機構の全容とAdipoRの糖脂質代謝・細胞ストレス改善における生物学的意義を解明し、受容体研究のブレイクスルーを目指す。また、認知症・動脈硬化症などの糖尿病合併症に対するAdipoRの抑制作用とそのメカニズムを解明する。さらに、AdipoRの立体構造・機能情報に基づいたAdipoR活性化低分子化合物の最適化や抗体医薬の開発による認知症などの多彩な合併症の抑制と健康長寿実現への基盤となる研究を展開する。
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| Outline of Final Research Achievements |
Given that the action of adiponectin and its receptors (AdipoRs) is shown to become diminished with the onset of obesity leading to the onset of metabolic syndrome, type 2 diabetes, and atherosclerosis. This research project has aimed to achieve new breakthroughs in AdipoR research through elucidation of novel mechanisms of action of AdipoR signal transduction and their biological implications in glucose/lipid metabolism as well as cell stress reduction. This promoted fundamental drug discovery research leading to the reduction of diabetic complications, such as dementia and atherosclerosis.
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病と合併症は、世界で激増しており、その原因解明と予防法・治療法開発は、喫緊の課題である。糖尿病は、細小血管症（網膜症、腎症、神経障害）や大血管症に加え、認知症やがんなどとも密接な関連が明らかとなってきた。これら多彩な合併症によって、健康寿命が短縮している。従って、動脈硬化症、特に認知症などの糖尿病合併症の病態解明と効果的な治療法開発は、超高齢社会において重要な課題であり、本研究成果の学術的意義および社会的意義は高いと考えられる。
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Report
(5 results)
Research Products
(39 results)
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[Journal Article] Human adiponectin receptor AdipoR1 assumes closed and open structures2020
Author(s)
Tanabe Hiroaki、Fujii Yoshifumi、Okada-Iwabu Miki、Iwabu Masato、Kano Kuniyuki、Kawana Hiroki、Hato Masakatsu、Nakamura Yoshihiro、Terada Takaho、Kimura-Someya Tomomi、Shirouzu Mikako、Kawano Yoshiaki、Yamamoto Masaki、Aoki Junken、Yamauchi Toshimasa、Kadowaki Takashi、Yokoyama Shigeyuki
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Journal Title
Communications Biology
Volume: 3
Issue: 1
Pages: 446-446
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Hepatic FATP5 expression is associated with histological progression and loss of hepatic fat in NAFLD patients2020
Author(s)
Enooku K, Tsutsumi T, Kondo M, Fujiwara N, Sasako T, Shibahara J, Kado A, Okushin K, Fujinaga H, Nakagomi R, Minami T, Sato M, Uchino K, Nakagawa H, Kondo Y, Asaoka Y, Tateishi R, Ueki K, Ikeda H, Yoshida H, Moriya K, Yotsuyanagi H, Kadowaki T, Koike K
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Journal Title
J Gastroenterol
Volume: 55
Issue: 2
Pages: 227-243
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Differential effects of diet- and genetically-induced brain insulin resistance on amyloid pathology in a mouse model of Alzheimer’s disease2019
Author(s)
Tomoko Wakabayashi, Kazuki Yamaguchi, Kentaro Matsui, Toshiharu Sano, Tetsuya Kubota, Tadafumi Hashimoto, Ayako Mano, Kaoru Yamada, Yuko Matsuo, Naoto Kubota, Takashi Kadowaki, Takeshi Iwatsubo
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Journal Title
Molecular Neurodegeneration
Volume: 14
Issue: 1
Pages: 15-15
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pivotal role of inter-organ aspartate metabolism for treatment of mitochondrial aspartate-glutamate carrier 2 (citrin) deficiency, based on the mouse model.2019
Author(s)
Saheki T, Moriyama M, Kuroda E, Funahashi A, Yasuda I, Setogawa Y, Gao Q, Ushikai M, Furuie S, Yamamura KI, Takano K, Nakamura Y, Eto K, Kadowaki T, Sinasac DS, Furukawa T, Horiuchi M, Tai YH.
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Journal Title
Sci Rep. 2019 Mar 12;9(1):4179.
Volume: 9 (1)
Issue: 1
Pages: 4179-4179
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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