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Modification of diabetic phenotype by Alzheimer's disease

Research Project

Project/Area Number 24659349
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field General internal medicine (including Psychosomatic medicine)
Research InstitutionOsaka University

Principal Investigator

SATO Naoyuki  大阪大学, 医学(系)研究科(研究院), 准教授 (70372612)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords糖尿病 / アルツハイマー病 / βアミロイド / 認知症 / 脳科学 / 分子生物学 / ベータ・アミロイド / 相互病態修飾 / 糖代謝
Research Abstract

We previously showed that Alzheimer's disease (AD) aggravates the diabetic phenotype in mice. To explore this mechanism, we initiated to create APP Tet-off mice. Plasma Abeta may mediate peripheral insulin resistance. We found plasma Abeta level is increased after glucose loading in an AD model. In humans, although the magnitude of changes is much smaller than in AD transgenic mice, the changes in plasma Abeta levels after oral glucose loading are different between AD and non-AD patients. These data suggest that one of the possible mechanisms by which AD aggravates the diabetic phenotype might be attributable to plasma Abeta. We are now constructing APP Tet-off plasmid and will create APP tet-off mice to control the periods of APP expression and exposure to diabetes.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (53 results)

All 2013 2012 Other

All Journal Article (12 results) (of which Peer Reviewed: 9 results) Presentation (36 results) (of which Invited: 6 results) Book (2 results) Remarks (3 results)

  • [Journal Article] Roles of Vascular and Metabolic Components in Cognitive Dysfunction of Alzheimer disease : Short- and Long-term Modification by Non-genetic Risk Factors2013

    • Author(s)
      Sato N and Morishita R
    • Journal Title

      Front. Aging Neurosci

      Volume: 5 Pages: 64-64

    • DOI

      10.3389/fnagi.2013.00064

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased Blood-Brain Barrier Vulnerability to Systemic Inflammation in Alzheimer Disease Mouse Model2013

    • Author(s)
      Shuko Takeda, Naoyuki Sato, Kazuko Ikimura, Hirohito Nishino, Hiromi Rakugi and Ryuichi Morishita
    • Journal Title

      Neurobiology of Aging

      Volume: (in press)

    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Journal Article] Plasma Abeta: A Possible Missing Link Between Alzheimer Disease and Diabetes2013

    • Author(s)
      Naoyuki Sato
    • Journal Title

      DIABETES

      Volume: 7 Issue: 4 Pages: 1005-1006

    • DOI

      10.2337/db12-1549

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Roles of Vascular and Metabolic Components in Cognitive Dysfunction of Alzheimer disease: Short- and Long-term Modification by Non-genetic Risk Factor2013

    • Author(s)
      Sato N* and Morishita R
    • Journal Title

      Front. Aging Neurosci.

      Volume: 5 Pages: 64-64

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased Blood-Brain Barrier Vulnerability to Systemic Inflammation in Alzheimer Disease Mouse Model.2013

    • Author(s)
      Shuko Takeda, Naoyuki Sato, Kazuko Ikimura, Hirohito Nishino, Hiromi Rakugi and Ryuichi Morishita.
    • Journal Title

      Neurobiology of Aging

      Volume: 34 Pages: 2064-70

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential regulation of amyloid precursor protein/presenilin 1 interaction during Ab40/42 production detected using fusion constructs2012

    • Author(s)
      Sato N
    • Journal Title

      PLoS One

      Volume: 7 Issue: 11 Pages: e48551-e48551

    • DOI

      10.1371/journal.pone.0048551

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Oral Glucose Loading Modulates Plasma β-Amyloid Level in Alzheimer's Disease Patients : Potential Diagnostic Method for Alzheimer's Disease.2012

    • Author(s)
      Shuko Takeda, et al.
    • Journal Title

      Dement Geriatr Cogn Disord

      Volume: 9;34(1) Issue: 1 Pages: 25-30

    • DOI

      10.1159/000338704

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of nucleic Acid drugs for neurological disorders2012

    • Author(s)
      Shimamura M, Sato N, Nakagami H, Taniyama Y, Morishita R.
    • Journal Title

      Curr Top Med Chem

      Volume: 12(15) Pages: 1621-9

    • Related Report
      2013 Final Research Report
  • [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
    • Journal Title

      FASEB J

      Volume: 26(6) Issue: 6 Pages: 2306-17

    • DOI

      10.1096/fj.11-196063

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of Central Nervous System Periostin in Cerebral Ischemia2012

    • Author(s)
      Munehisa Shimamura
    • Journal Title

      Stroke

      Volume: 43 Issue: 4 Pages: 1108-1114

    • DOI

      10.1161/strokeaha.111.636662

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dual effects of statins on Aβ metabolism: upregulation of the degradation of APP-CTF and Aβ clearance2012

    • Author(s)
      Sato N
    • Journal Title

      Neurodegener Dis

      Volume: 10 Issue: 1-4 Pages: 305-308

    • DOI

      10.1159/000334534

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Possible Modification of Alzheimer Disease by Statins in Midlife : Interactions with Genetic and Non-Genetic Risk Factors

    • Author(s)
      Mitsuru Shinohara, Naoyuki Sato, Munehisa Shimamura, Hitomi Kurinami, Toshimitsu Hamasaki, Amarnath Chatterjee, Hiromi Rakugi, Ryuichi Morishita
    • Journal Title

      Front Aging Neurosci

      Volume: (In press)

    • Related Report
      2013 Final Research Report
  • [Presentation] Diabetes Disrupts Homeostasis against Alzheimer's Disease2013

    • Author(s)
      Naoyuki Sato
    • Organizer
      Asia-Pacific Diabetes and Obesity Study Group (APDO) symposium 2013
    • Place of Presentation
      Tokyo
    • Year and Date
      2013-10-12
    • Related Report
      2013 Final Research Report
  • [Presentation] シンポジウム3「生活習慣病と認知症」"糖尿病とアルツハイマー病の発症機構"2013

    • Author(s)
      里 直行
    • Organizer
      第3回日本認知症予防学会
    • Place of Presentation
      新潟
    • Year and Date
      2013-09-29
    • Related Report
      2013 Final Research Report
  • [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
      2013 Final Research Report
  • [Presentation] 最優秀演題賞"糖尿病はアルツハイマー病において恒常性維持機構を破綻させる"2013

    • Author(s)
      里 直行
    • Organizer
      第13回日本抗加齢医学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2013-06-29
    • Related Report
      2013 Final Research Report
  • [Presentation] シンポジウム5「体内老化因子」"アルツハイマー病と糖尿病の相互作用における体内老化因子"2013

    • Author(s)
      里 直行
    • Organizer
      第13回日本抗加齢医学会総会
    • Place of Presentation
      横
    • Year and Date
      2013-06-28
    • Related Report
      2013 Final Research Report
  • [Presentation] 長期的な高脂肪食負荷はアルツハイマー病モデルマウスにおいて血中βアミロイドを増加させる2013

    • Author(s)
      里 直行、樂木宏実、森下竜一
    • Organizer
      第28回日本老年学会総会・第55回日本老年医学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2013-06-06
    • Related Report
      2013 Final Research Report
  • [Presentation] 糖尿病はアルツハイマー病モデルマウス脳においてタウのリン酸化を促進する2013

    • Author(s)
      里 直行、田中稔久、村山繁雄、武田雅俊、樂木宏実、森下竜一
    • Organizer
      第28回日本老年学会総会・第55回日本老年医学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2013-06-05
    • Related Report
      2013 Final Research Report
  • [Presentation] βアミロイド産生機構 : アミロイド前駆体蛋白とプレセニリンの融合蛋白を用いた解析2013

    • Author(s)
      里 直行、武田雅俊、樂木宏実、森下竜一
    • Organizer
      第28回日本老年学会総会・第55回日本老年医学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2013-06-05
    • Related Report
      2013 Final Research Report
  • [Presentation] ランチョン・セミナー"後天的危険因子からみたアルツハイマー病の解析"2013

    • Author(s)
      里 直行
    • Organizer
      第28回日本老年学会総会・第55回日本老年医学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2013-06-04
    • Related Report
      2013 Final Research Report
  • [Presentation] Symposia S16 : Strategies on biomarkers to diagnose Alzheimer's disease. Chair : Laura Morelli. "Role of adult common desease in the development of Alzheimer disease : Application to diagnostic and therapeutic indication"2013

    • Author(s)
      Naoyuki Sato, Ryuichi Morishita
    • Organizer
      24th Biennial Joint Meeting, International society for Neurochemistry, American Society for Neurochemistry
    • Place of Presentation
      Cancun, Mexico
    • Year and Date
      2013-04-22
    • Related Report
      2013 Final Research Report
  • [Presentation] Symposium 7 : Pathophysiology and therapeutics for dysfunction of higher brain function in metabolic disease. "How does diabetes mellitus increase the incidence of Alzheimer's disease?"2013

    • Author(s)
      Naoyuki Sato
    • Organizer
      The 86th Annual Meeting of The Japanese Pharmacological Society
    • Place of Presentation
      Fukuoka
    • Year and Date
      2013-03-21
    • Related Report
      2013 Final Research Report
  • [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
      2013-03-10
    • Related Report
      2013 Final Research Report
  • [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 11 th International Conference on Alzheimer's & Parkinson's Diseases AD/PD 2013
    • Place of Presentation
      Italy
    • Year and Date
      2013-03-10
    • Related Report
      2013 Final Research Report
  • [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
      2013-03-09
    • Related Report
      2013 Final Research Report
  • [Presentation] Abeta is prerequisite, but insufficient to cause tau phosphorylation in vivo : tau phosphorylation in APP mice by diabetes (POSTER PRIZE - 2nd Prize)2013

    • Author(s)
      Naoyuki Sato
    • Organizer
      3rd International Conference on Molecular Neurodegeneration -Basic biology and disease pathways
    • Place of Presentation
      Cannes, France
    • Related Report
      2013 Final Research Report
  • [Presentation] Abeta is prerequisite, but insufficient to cause tau phosphorylation in vivo: tau phosphorylation in APP mice by diabetes2013

    • Author(s)
      Naoyuki Sato
    • Organizer
      3rd International Conference on Molecular Neurodegeneration - Basic biology and disease pathways
    • Place of Presentation
      France
    • Related Report
      2013 Annual Research Report
  • [Presentation] Tau phosphorylation is ncreased 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
      2013 Final Research Report
  • [Presentation] Amyloid Precursor Protein/Presenilin 1 Interaction is Differentially Regulated during A1340/42 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
      2013 Final Research Report
  • [Presentation] シンポジウム「脂質異常症の抗加齢医療」脂質異常症、スタチンとアルツハイマー病"n2012

    • Author(s)
      里 直行
    • Organizer
      脳心血管抗加齢研究会2012
    • Place of Presentation
      大阪
    • Year and Date
      2012-11-18
    • Related Report
      2013 Final Research Report
  • [Presentation] シンポジウム「Common diseaseの体質と環境」"認知症の体質と環境"2012

    • Author(s)
      里 直行
    • Organizer
      第62回日本体質医学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2012-11-04
    • Related Report
      2013 Final Research Report
  • [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
      2013 Final Research Report
  • [Presentation] Old APPxob/ob mice showed highly increased level of tau phosphorylation in brain2012

    • 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
      Neuroscience 2012
    • Place of Presentation
      New Orleans
    • Year and Date
      2012-10-15
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [Presentation] シンポジウム3「生活習慣病と認知症」"生活習慣病がアルツハイマー病病理および血管病変に与える影響"2012

    • Author(s)
      里 直行
    • Organizer
      VAS-COG JAPAN 2012
    • Place of Presentation
      東
    • Year and Date
      2012-09-08
    • Related Report
      2013 Final Research Report
  • [Presentation] 認知症の危険因子と予防療法2012

    • Author(s)
      里 直行
    • Organizer
      第53回日本神経学会学術大会、シンポジウム「認知症疫学研究が提供するエビデンス」
    • Place of Presentation
      東京
    • Year and Date
      2012-05-23
    • Related Report
      2013 Final Research Report
  • [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. Chair: Jie Shen, Vice Chair: Joachim J. Herz
    • Place of Presentation
      Stonehill College
    • Related Report
      2013 Final Research Report
  • [Presentation] Roles of beta-amyloid and insulin resistance in the interaction between diabetes mellitus and Alzheimer's disease2012

    • Author(s)
      Naoyuki Sato
    • Organizer
      Gordon Research Conferences, Neurobiology of Brain Disorders
    • Place of Presentation
      Stonehill
    • Related Report
      2012 Research-status Report
  • [Presentation] Molecular Mechanisms Linking Alzheimer's Disease And Its Non-Genetic Risk Factors - Towards Novel Therapeutic Strategies (SS24 517-B). 1. Pathological interaction between Alzheimer's disease and diabetes mellitus Naoyuki Sato

    • Author(s)
      Chairs: Naoyuki Sato, Makoto Higuchi
    • Organizer
      The 20th IAGG World Congress of Gerontology and Geriatrics
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2013 Final Research Report
  • [Presentation] Pathological interaction between Alzheimer's disease and diabetes mellitus

    • Author(s)
      Naoyuki Sato
    • Organizer
      The 20th IAGG World Congress of Gerontology and Geriatrics
    • Place of Presentation
      korea
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Role of adult common desease in the development of Alzheimer disease: Application to diagnostic and therapeutic indication

    • Author(s)
      Naoyuki Sato, Ryuichi Morishita
    • Organizer
      24th Biennial Joint Meeting, International society for Neurochemistry, American Society for Neurochemistry
    • Place of Presentation
      Mexico
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 糖尿病とアルツハイマー病の発症機構

    • Author(s)
      里 直行
    • Organizer
      第3回日本認知症予防学会
    • Place of Presentation
      新潟
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] アルツハイマー病と糖尿病の相互作用における体内老化因子

    • Author(s)
      里 直行
    • Organizer
      第13回日本抗加齢医学会総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] How does diabetes mellitus increase the incidence of Alzheimer's disease?

    • Author(s)
      Naoyuki Sato
    • Organizer
      The 86th Annual Meeting of The Japanese Pharmacological Society
    • Place of Presentation
      Fukuoka
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Diabetes increases tau phosphorylation in APP mice: evidence that Abeta is prerequisite, but insufficient to cause tau phosphorylatio

    • Author(s)
      Naoyuki Sato
    • Organizer
      The 11th International Conference on Alzheimer's & Parkinson's Diseases AD/PD 2013
    • Place of Presentation
      Italy
    • Related Report
      2012 Research-status Report
  • [Presentation] The mechanisms by which diabetes mellitus increases the risk of Alzheimer's disease

    • Author(s)
      Naoyuki Sato
    • Organizer
      Keystone Symposia, Aging and Diseases of Aging
    • Place of Presentation
      Tokyo
    • Related Report
      2012 Research-status Report
  • [Presentation] 認知症の体質と環境

    • Author(s)
      里 直行
    • Organizer
      第62回日本体質医学会総会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
    • Invited
  • [Book] Aβ Deposition, Insulin Signaling, and Tau Phosphorylation in Animal Models of Alzheimer Disease and Diabetes. Metabolic Syndrome and Neurological Disorders2013

    • Author(s)
      Naoyuki Sato and Ryuichi Morishita
    • Publisher
      Akhlaq A. Farooqui , Tahira Farooqui. John Wiley & Sons
    • Related Report
      2013 Final Research Report
  • [Book] Metabolic Syndrome and Neurological Disorders. Eds: Akhlaq A. Farooqui , Tahira Farooqui.2013

    • Author(s)
      Naoyuki Sato and Ryuichi Morishita
    • Total Pages
      12
    • Publisher
      John Wiley & Sons
    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://www.cgt.med.osaka-u.ac.jp/

    • Related Report
      2013 Final Research Report
  • [Remarks] 大阪大学大学院医学系研究科臨床遺伝子治療学 里 直行

    • Related Report
      2013 Annual Research Report
  • [Remarks] 大阪大学臨床遺伝子治療学

    • URL

      http://www.cgt.med.osaka-u.ac.jp/

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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