| Project/Area Number |
17K09816
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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 | Tohoku University |
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Principal Investigator |
Imai Junta 東北大学, 医学系研究科, 准教授 (80431500)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 膵β細胞 / インスリン / 迷走神経 / 糖尿病 / 肥満症 |
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| Outline of Final Research Achievements |
Previously, we discovered that pancreatic vagal nerve signals, elicited by liver-β cell inter-organ neuronal network, play critical roles in triggering compensatory β cell proliferation during obesity development. In this project, we explored the molecular mechanism(s) by which vagal signals enhance β cell proliferation. The FoxM1 pathway was activated in pancreatic islets of obese mice, and β cell proliferation induced by obesity was blocked in β cell specific FoxM1 knockout mice. Suppression of the neuronal network blocked activation of β cell FoxM1 and thereby suppressed β cell proliferation in obese mice. Furthermore, combined treatment of pancreatic islets with pancreatic vagus-producing factors, such as acetylcholine and PACAP/VIP, activated the FoxM1 pathway and enhanced β cell proliferation, and these effects were abolished in islets from FoxM1βKO mice. These results demonstrate how vagal signals induce compensatory β cell proliferation in obesity settings.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は研究代表者が独自に明らかにした肝臓―膵β細胞間神経ネットワークに着想を得て、膵迷走神経による膵β細胞増殖制御の分子メカニズムを明らかにしたものである。現在のところ、膵β細胞を増量する治療法は存在せず、これは糖尿病根治療法開発が進まない大きな要因となっている。迷走神経由来因子による膵β細胞増殖機構を明らかにしたことで、世界で初めての膵β細胞増量薬の開発につながる可能性がある。
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