Modification of diabetic phenotype by Alzheimer's disease

阿尔茨海默病对糖尿病表型的改变

• 批准号: 24659349
• 负责人: SATO Naoyuki
• 金额: $ 2万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659349/
• 关键词: 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

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.

我们先前表明，阿尔茨海默氏病（AD）在小鼠中表现为糖尿病表型。为了探索这一机制，我们开始创建APP Tet-off小鼠。血浆A β可能介导外周胰岛素抵抗。我们发现在AD模型中，葡萄糖负荷后血浆Abeta水平升高。在人类中，虽然变化幅度远小于AD转基因小鼠，但AD和非AD患者口服葡萄糖负荷后血浆Abeta水平的变化不同。这些数据表明，AD使糖尿病表型恶化的可能机制之一可能归因于血浆Abeta。我们现在正在构建APP Tet-off质粒，并将创建APP tet-off小鼠以控制APP表达和暴露于糖尿病的时间。

项目成果

Diabetes increases tau phosphorylation in APP mice: evidence that Abeta is prerequisite, but insufficient to cause tau phosphorylation

糖尿病增加 APP 小鼠的 tau 磷酸化：证据表明 Abeta 是先决条件，但不足以引起 tau 磷酸化

• 作者: Ueno N;Fujiya M;Segawa S;Nata T;Inaba Y;Moriichi K;Tanabe H;Mizukami. Y;Kobayashi N;Ito K;Kohgo Y.;Naoyuki Sato
• 通讯作者: Naoyuki Sato

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"

最佳演讲奖：“糖尿病破坏阿尔茨海默病的体内平衡”

• 发表时间: 2013
• 作者: Naoyuki Sato;Mari Mori-Ueda;Toshihisa Tanaka;Shuko Takeda;Kozue Uchio-Yamada;Hironori Ueda;Mitsuru Shinohara;Shigeo Murayama;Masatoshi Takeda;Hiromi Rakugi;Ryuichi Morishita;里 直行
• 通讯作者: 里 直行

Tau phosphorylation is ncreased by diabetes mellitus in APP transgenic mice

APP 转基因小鼠糖尿病导致 Tau 磷酸化增加

• 发表时间: 2012
• 作者: Naoyuki Sato;Mari Mori-Ueda;Toshihisa Tanaka;Shuko Takeda;Kozue Uchio-Yamada;Hironori Ueda;Mitsuru Shinohara;Shigeo Murayama;Masatoshi Takeda;Hiromi Rakugi;Ryuichi Morishita
• 通讯作者: Ryuichi Morishita

認知症の危険因子と予防療法

痴呆症危险因素和预防治疗

• 发表时间: 2012
• 作者: Naoyuki Sato;Mari Mori-Ueda;Toshihisa Tanaka;Shuko Takeda;Kozue Uchio-Yamada;Hironori Ueda;Mitsuru Shinohara;Shigeo Murayama;Masatoshi Takeda;Hiromi Rakugi;Ryuichi Morishita;里 直行;里 直行
• 通讯作者: 里 直行

認知症の体質と環境

痴呆症的体质与环境

• 作者: Naoyuki Sato;Ryuichi Morishita;里 直行;里 直行;Naoyuki Sato;Naoyuki Sato;Naoyuki Sato;里 直行
• 通讯作者: 里 直行