Modification of diabetic phenotype by Alzheimer's disease

• Project/Area Number: 24659349
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: General internal medicine (including Psychosomatic medicine)
• Research Institution: Osaka 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: ¥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.

Research Products

• [Journal Article] Roles of Vascular and Metabolic Components in Cognitive Dysfunction of Alzheimer disease : Short- and Long-term Modification by Non-genetic Risk Factors (2013)
  • Author(s): Sato N and Morishita R
  • Journal Title: Front. Aging Neurosci Volume: 5 Pages: 64-64
  • DOI: 10.3389/fnagi.2013.00064
  • 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: (in press)
• [Journal Article] Plasma Abeta: A Possible Missing Link Between Alzheimer Disease and Diabetes (2013)
  • Author(s): Naoyuki Sato
  • Journal Title: DIABETES Volume: 7 Issue: 4 Pages: 1005-1006
  • DOI: 10.2337/db12-1549
  • 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 Factor (2013)
  • Author(s): Sato N* and Morishita R
  • Journal Title: Front. Aging Neurosci. Volume: 5 Pages: 64-64
  • 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
  • Peer Reviewed
• [Journal Article] Differential regulation of amyloid precursor protein/presenilin 1 interaction during Ab40/42 production detected using fusion constructs (2012)
  • Author(s): Sato N
  • Journal Title: PLoS One Volume: 7 Issue: 11 Pages: e48551-e48551
  • DOI: 10.1371/journal.pone.0048551
  • 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
  • Peer Reviewed
• [Journal Article] Development of nucleic Acid drugs for neurological disorders (2012)
  • Author(s): Shimamura M, Sato N, Nakagami H, Taniyama Y, Morishita R.
  • Journal Title: Curr Top Med Chem Volume: 12(15) Pages: 1621-9
• [Journal Article] a novel regulator of mitochondrial γ-secretase, maintains normal mitochondrial function (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Role of Central Nervous System Periostin in Cerebral Ischemia (2012)
  • Author(s): Munehisa Shimamura
  • Journal Title: Stroke Volume: 43 Issue: 4 Pages: 1108-1114
  • DOI: 10.1161/strokeaha.111.636662
  • Peer Reviewed
• [Journal Article] Dual effects of statins on Aβ metabolism: upregulation of the degradation of APP-CTF and Aβ clearance (2012)
  • Author(s): Sato N
  • Journal Title: Neurodegener Dis Volume: 10 Issue: 1-4 Pages: 305-308
  • DOI: 10.1159/000334534
  • 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)
• [Presentation] Diabetes Disrupts Homeostasis against Alzheimer's Disease (2013)
  • 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
• [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
• [Presentation] Possible involvements of Abeta, insulin signaling and tau phosphorylation in the pathological interaction between Alzheimer disease and diabetes (2013)
  • 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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [Presentation] Diabetes increases tau phosphorylation in APP mice : evidence that Abeta is prerequisite, but insufficient to cause tau phosphorylation (2013)
  • 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
• [Presentation] Diabetes increases tau phosphorylation in APP mice : evidence that Abeta is prerequisite, but insufficient to cause tau phosphorylation (2013)
  • 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
• [Presentation] Amyloid precursor protein/presenilin 1 interaction is differentially regulated during Abeta40/42 production : detection using fusion constructs (2013)
  • 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
• [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
• [Presentation] Abeta is prerequisite, but insufficient to cause tau phosphorylation in vivo: tau phosphorylation in APP mice by diabetes (2013)
  • Author(s): Naoyuki Sato
  • Organizer: 3rd International Conference on Molecular Neurodegeneration - Basic biology and disease pathways
  • Place of Presentation: France
• [Presentation] Tau phosphorylation is ncreased by diabetes mellitus in APP transgenic mice (2012)
  • 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
• [Presentation] Amyloid Precursor Protein/Presenilin 1 Interaction is Differentially Regulated during A1340/42 Production : Detection Using Fusion Constructs (2012)
  • 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
• [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"n (2012)
  • 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
• [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
• [Presentation] The mechanisms by which diabetes mellitus increases the risk of Alzheimer's disease (2012)
  • 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
• [Presentation] Old APPxob/ob mice showed highly increased level of tau phosphorylation in brain (2012)
  • 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
• [Presentation] The mechanism by which diabetes mellitus increase the risk of Alzheimer disease (2012)
  • 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
• [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
• [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
• [Presentation] Roles of beta-amyloid and insulin resistance in the interaction between diabetes mellitus and Alzheimer's disease (2012)
  • 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
• [Presentation] Roles of beta-amyloid and insulin resistance in the interaction between diabetes mellitus and Alzheimer's disease (2012)
  • Author(s): Naoyuki Sato
  • Organizer: Gordon Research Conferences, Neurobiology of Brain Disorders
  • Place of Presentation: Stonehill
• [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
• [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
  • 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
  • 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
  • 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
  • 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
  • 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
• [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
• [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
  • Invited
• [Book] Aβ Deposition, Insulin Signaling, and Tau Phosphorylation in Animal Models of Alzheimer Disease and Diabetes. Metabolic Syndrome and Neurological Disorders (2013)
  • Author(s): Naoyuki Sato and Ryuichi Morishita
  • Publisher: Akhlaq A. Farooqui , Tahira Farooqui. John Wiley & Sons
• [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
• [Remarks]
  • URL: http://www.cgt.med.osaka-u.ac.jp/
• [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
• [Remarks] 大阪大学臨床遺伝子治療学
  • URL: http://www.cgt.med.osaka-u.ac.jp/