2023 Fiscal Year Final Research Report
Elucidation of molecular mechanisms of growth, aging, and glucose metabolism control by the central nervous system
| Project/Area Number |
21K16347
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | The University of Tokyo (2023)
National Institutes of Biomedical Innovation, Health and Nutrition (2021-2022) |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | インスリン受容体基質-1 / 成長 / 中枢神経 |
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| Outline of Final Research Achievements |
Although insulin and IGF-1 signaling in the central nervous system have been reported to be involved in glucose metabolism, growth, and lifespan, the molecular mechanisms of these signals, especially the role of Irs1, a major intracellular substrate of both signals, in the central nervous system is unknown. In this study, we generated brain-specific Irs1-deficient mice. These mice showed growth retardation with reduced expression of GRHR in hypothalamus. Moreover, these mice exhibited increased insulin sensitivity and glucose utilization in the skeletal muscle. In vitro, neurite elongation after IGF-1 stimulation was significantly impaired by Irs1 downregulation in the cultured hypothalamic neurons. These data suggest that Irs1 plays important roles in the regulation of neurite outgrowth of GHRH neurons, somatic growth, and glucose homeostasis.
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| Free Research Field |
糖尿病
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では2系統の異なる脳特異的Irs1欠損マウスを独自に作成しその解析を行っており、類似の研究結果は国内外を含め発表されていない。今回の研究で我々は中枢のIrs1が神経の伸長や糖代謝に関与することを明らかとした。今後さらに中枢のIrs1の病態生理学的役割の解明へと研究を発展させることで、脳虚血や脳外傷、神経変性疾患、糖尿病等の疾患の病態解明や治療につながる可能性が期待される。
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