| Project/Area Number |
17K09833
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
前田 泰孝 九州大学, 大学病院, 助教 (00621377)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | GLP-1 / 単球 / 炎症 / 心筋 / 臓器保護効果 / GLP-1受容体 / 神経ペプチド / 炎症制御因子 / グルカゴン様ペプチド1 / glucagon like peptide-1 / GLP-1（グルカゴン様ペプチド1） / 糖尿病 / ノックアウトマウス |
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| Outline of Final Research Achievements |
In the present study, we developed neuronal and monocyte-specific GLP-1 receptor deficient mice. We especially focused on monocyte-specific GLP-1 receptor deficient mice. Monocyte-specific GLP-1 receptor deficient mice seemed to develop normally and showed no obvious metabolic abnormality, but has diastolic dysfunction from about age 18-week compared with the control group. It was confirmed myocardial fibrosis progresses at the tissue and gene level at this time. From these findings, it was considered that GLP-1 exerts an organ-protecting effect by controlling inflammation including fibrosis as a physiological action of GLP-1 mediated by monocytes. It is suggested that this is one of the mechanisms of cardiovascular protective action of GLP-1 receptor agonists which is clinically recognized.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により消化管ホルモンであるGLP-1の生理的役割の新たな一端が明らかとなった。これまで人における心保護作用の少なくとも一部は単球に発現するGLP-1受容体の抗炎症、抗線維化作用を介することを初めて明らかにした。その詳細な機序は今後の課題であるが、食事依存性に分泌されるホルモンであるGLP-1が臓器間ネットワークを介して多臓器へ作用を及ぼすメカニズムの解明が進めば、現在、臨床応用されている抗糖尿病薬としてのみならず、他の代謝疾患や炎症性疾患などにも臨床応用が可能となり、治療法が確立されていない多くの疾患への応用が期待される。
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