2010 Fiscal Year Final Research Report
Role of lipid phosphatase in brain insulin resistance related to neuroprotection and memory function
| 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
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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 |
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| 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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[Journal Article] The inositol phosphatase SHIP2 negatively regulates insulin/IGF-1actions implicated in neuroprotection and memory function in mouse brain.2010
Author(s)
Soeda Y, Tsuneki H, Muranaka H, Mori N, Hosoh S, Ichihara Y, Kagawa S, Wang X, Toyooka N, Uwano T, Nishijo H, Wada T,Sasaoka T.
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Journal Title
Molecular Endocrinology 24
Pages: 1965-1977
Peer Reviewed
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