| Project/Area Number |
20591053
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | University of Toyama |
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Principal Investigator |
SASAOKA Toshiyasu University of Toyama, 大学院・医学薬学研究部(薬学), 教授 (00272906)
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| Co-Investigator(Kenkyū-buntansha) |
TSUNEKI Hiroshi 富山大学, 大学院・医学薬学研究部, 准教授 (20332661)
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| Project Period (FY) |
2008 – 2010
|
| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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|---|
| Keywords | エネルギー・糖代謝異常 / インスリン作用 / 認知機能 / ホスファターゼ / 認知障害 / ボスファターゼ / SHIP2 / PI3-キナーゼ / PTEN / 神経変性 |
|---|
| Research Abstract |
Although brain insulin resistance is a cause of cognitive impairment associated with type 2 diabetes and Alzheimer's disease, the precise underlying mechanism is largely unknown. In the present study, we found that lipid phosphatase SHIP2, a negative regulator of insulin signaling, is increased in the brain of type 2 diabetic db/db and aged mice. Mice overexpressing SHIP2 exhibited impaired memory performance with disrupted insulin signaling and increased apoptosis in the brain. Importantly, inhibition of SHIP2 ameliorated the impairment of hippocampal synaptic plasticity and memory formation in db/db mice. These results suggest that inhibition of SHIP2 is a novel therapeutic approach in brain dysfunction related to insulin resistance with type 2 diabetes.
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