The roles of insulin signaling between diabetes and Alzheimer's disease
| Project/Area Number |
23390187
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General internal medicine (including Psychosomatic medicine)
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| Research Institution | Osaka University |
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Principal Investigator |
SATO Naoyuki 大阪大学, 医学(系)研究科(研究院), 准教授 (70372612)
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| Co-Investigator(Kenkyū-buntansha) |
UCHIO Kozue 医薬基盤研究所, 難病・疾患資源研究部, 主任研究員 (70373397)
UEDA Hironori 大阪大学, 医学研究科, 特任准教授 (90543463)
MURAYAMA Shigeo 東京都健康長寿医療センター, 研究部長 (50183653)
林 真一郎 独立行政法人国立循環器病研究センター, その他部局等, 研究員 (20396740)
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| Co-Investigator(Renkei-kenkyūsha) |
HAYASHI Shinichiro 国立循環器病センター, 病院, 医師 (20396740)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2013: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2012: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2011: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
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| Keywords | 糖尿病 / アルツハイマー病 / 神経科学 / 分子生物学 / 病理学 / 認知症 / 脳科学 / ベータ・アミロイド / タウ・リン酸化 / 恒常性破綻 / βアミロイド / インスリン・シグナル / タウ / 老人斑 / 神経原線維変化 |
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| Research Abstract |
Epidemiological studies suggest that diabetes mellitus increases the risk of onset of Alzheimer disease (AD). However, the underlying mechanisms have not been fully understood. Six months on a high fat diet increased Abeta40 in B6C mice brain. To investigate the effects of diabetes on AD, we further analyzed the phenotypes of APP+ob/ob mice, which showed the increased cerebral amyloid angiopathy and impaired insulin signaling, especially focusing on tau phosphorylation. 18 month old APP+ob/ob mice showed highly increased level of tau phosphorylation in the brain. Tau phosphorylation is increased by diabetes in APP mice, suggesting that Abeta is prerequisite, but insufficient to cause tau phosphorylation in vivo. Abeta accumulation, insulin signaling and tau phosphorylation might play essential roles in the pathological interaction between AD and diabetes.These results suggest that diabetes disrupts homeostasis against AD.
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Report
(4 results)
Research Products
(77 results)
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[Journal Article] a novel regulator of mitochondrial γ-secretase, maintains normal mitochondrial function2012
Author(s)
Hayashi H, Nakagami H, Takeichi M, Shimamura M, Koibuchi N, Oiki E, Sato N, Koriyama H, Mori M, Gerardo Araujo R, Maeda A, Morishita R, Tamai K, Kaneda Y. HIG1
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Journal Title
FASEB J
Volume: 26(6)
Issue: 6
Pages: 2306-17
DOI
Related Report
Peer Reviewed
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[Journal Article] HIG1, a novel regulator of mitochondrial γ-secretase, maintains normal mitochondrial function2012
Author(s)
Hayashi H, Nakagami H, Takeichi M, Shimamura M, Koibuchi N, Oiki E, Sato N, Koriyama H, Mori M, Gerardo Araujo R, Maeda A, Morishita R, Tamai K, Kaneda Y
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Journal Title
FASEB J
Volume: (In press)
Related Report
Peer Reviewed
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[Presentation] Possible involvements of Abeta, insulin signaling and tau phosphorylation in the pathological interaction between Alzheimer disease and diabetes2013
Author(s)
Naoyuki Sato, Mari Mori-Ueda, Toshihisa Tanaka, Shuko Takeda, Kozue Uchio-Yamada, Hironori Ueda, Mitsuru Shinohara, Shigeo Murayama, Masatoshi Takeda, Hiromi Rakugi, Ryuichi Morishita
Organizer
AAIC 2013 The Alzheimer's Association International Conference 2013
Place of Presentation
Boston
Year and Date
2013-07-14
Related Report
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[Presentation] Diabetes increases tau phosphorylation in APP mice : evidence that Abeta is prerequisite, but insufficient to cause tau phosphorylation2013
Author(s)
N Sato, M Mori-Ueda, T Tanaka, S Takeda, K Uchio-Yamada, H Ueda, M Shinohara, S Murayama, M Takeda, H Rakugi, R Morishita
Organizer
The 11th International Conference on Alzheimer's & Parkinson's Diseases AD/PD 2013
Place of Presentation
Italy
Year and Date
2013-02-10
Related Report
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[Presentation] Amyloid precursor protein/presenilin 1 interaction is differentially regulated during Abeta40/42 production : detection using fusion constructs2013
Author(s)
N Sato, M Okochi, M Shinohara, G Thinakaran, S Takeda, A Fukumori, M Shinohara-Noma, M Mori-Ueda, H Hamada, M Takeda, H Rakugi, R Morishita
Organizer
The 11th International Conference on Alzheimer's & Parkinson's Diseases AD/PD 2013
Place of Presentation
Italy
Year and Date
2013-02-09
Related Report
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[Presentation] Tau phosphorylation is increased by diabetes mellitus in APP transgenic mice2012
Author(s)
Naoyuki Sato, Mari Mori-Ueda, Toshihisa Tanaka, Shuko Takeda, Kozue Uchio-Yamada, Hironori Ueda, Mitsuru Shinohara, Shigeo Murayama, Masatoshi Takeda, Hiromi Rakugi, Ryuichi Morishita
Organizer
The 17th Takeda Science Foundation Symposium on Bioscience
Place of Presentation
Osaka
Year and Date
2012-12-07
Related Report
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[Presentation] Amyloid Precursor Protein/Presenilin 1 Interaction is Differentially Regulated during Aβ40/42 Production : Detection Using Fusion Constructs2012
Author(s)
Naoyuki Sato, Masayasu Okochi, Mitsuru Shinohara, Gopal Thinakaran, Shuko Takeda, Akio Fukumori, Motoko Shinohara-Noma, Mari Mori-Ueda, Hizuki Hamada, Masatoshi Takeda, Hiromi Rakugi, Ryuichi Morishita
Organizer
The 17th Takeda Science Foundation Symposium on Bioscience
Place of Presentation
Osaka
Year and Date
2012-12-07
Related Report
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[Presentation] The mechanisms by which diabetes mellitus increases the risk of Alzheimer's disease2012
Author(s)
Naoyuki Sato, Mari Mori-Ueda, Toshihisa Tanaka, Shuko Takeda, Kozue Uchio-Yamada, Hironori Ueda, Mitsuru Shinohara, Shigeo Murayama, Masatoshi Takeda, Hiromi Rakugi, Ryuichi Morishita
Organizer
Keystone Symposia, Aging and Diseases of Aging
Place of Presentation
Tokyo
Year and Date
2012-10-25
Related Report
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[Presentation] The mechanism by which diabetes mellitus increase the risk of Alzheimer disease2012
Author(s)
Naoyuki Sato, Mari Mori-Ueda, Toshihisa Tanaka, Shuko Takeda, Kozue Uchio-Yamada, Hironori Ueda, Mitsuru Shinohara, Shigeo Murayama, Masatoshi Takeda, Hiromi Rakugi, Ryuichi Morishita
Organizer
Neuroscience2012
Place of Presentation
Nagoya
Year and Date
2012-09-18
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[Presentation] Roles of beta-amyloid and insulin resistance in the interaction between diabetes mellitus and Alzheimer's disease2012
Author(s)
Naoyuki Sato, Mari Mori-Ueda, Toshihisa Tanaka, Shuko Takeda, Kozue Uchio-Yamada, Hironori Ueda, Mitsuru Shinohara, Shigeo Murayama, Masatoshi Takeda, Hiromi Rakugi, Ryuichi Morishita
Organizer
Gordon Research Conferences, Neurobiology of Brain Disorders
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