Comprehensive analysis of the mechanisms of pancreatic beta cell proliferation by vagal nerve signals for therapeutic application
| Project/Area Number |
18K16221
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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 | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 迷走神経 / 膵β細胞 / 肝臓 / 再生医療 / 自律神経 / 臓器間ネットワーク / 糖尿病 / 肥満症 |
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| Outline of Final Research Achievements |
In this project, we explored the molecular mechanisms of vagal nerve signal-mediated cell proliferation and organ regeneration and its therapeutic potential in pancreatic beta cells and the liver. First, we applied a tissue-clearing technology to the pancreas in order to analyze the anatomy of the vagal nerve system within the pancreas. We found that many of intra-pancreatic parasympathetic ganglia are located in the vicinity of islets. Next, we tested whether vagal nerve signals could induce beta cell proliferation in aged animals, in which cell proliferation capacity is known to be severely restricted. We found that high fat diet feeding promoted beta cell proliferation and increased beta cell mass through vagal nerve signals even in aged mice. Moreover, we clarified that vagal nerve signals are critically involved in liver regeneration after partial hepatectomy and elucidated the molecular mechanism by which vagal nerve signals induce hepatocyte proliferation.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、研究代表者が所属するグループが見出した神経シグナルを介した細胞増殖誘導機構と、それによる生体の恒常性維持機構の詳細について、膵β細胞と肝臓を用いて明らかにした。神経シグナルによる細胞増殖機構を臨床に応用することで、高齢者に多い膵β細胞が減少することで発症する糖尿病や、肝臓切除後の肝不全などに対する有望な予防、治療法の開発につながることが期待される。
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Report
(3 results)
Research Products
(5 results)
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[Journal Article] Vagus-macrophage-hepatocyte link promotes post-injury liver regeneration and whole-body survival through hepatic FoxM1 activation.2018
Author(s)
Izumi T, Imai J, Yamamoto J, Kawana Y, Endo A, Sugawara H, Kohata M, Asai Y, Takahashi K, Kodama S, Kaneko K, Gao J, Uno K, Sawada S, Kalinichenko VV, Ishigaki Y, Yamada T, Katagiri H.
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Journal Title
Nat Commun.
Volume: 9
Issue: 1
Pages: 5300-5300
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Serum cystatin C level is associated with carotid arterial wall elasticity in subjects with type 2 diabetes mellitus: A potential marker of early-stage atherosclerosis.2018
Author(s)
Kaneko R, Sawada S, Tokita A, Honkura R, Tamura N, Kodama S, Izumi T, Takahashi K, Uno K, Imai J, Yamada T, Miyachi Y, Hasegawa H, Kanai H, Ishigaki Y, Katagiri H
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Journal Title
Diabetes Research and Clinical Practice
Volume: 139
Pages: 43-51
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Selective insulin resistance with differential expressions of IRS-1 and IRS-2 in human NAFLD livers.2018
Author(s)
Honma M, Sawada S, Ueno Y, Murakami K, Yamada T, Gao J, Kodama S, Izumi T, Takahashi K, Tsukita S, Uno K, Imai J, Kakazu E, Kondo Y, Mizuno K, Kawagishi N, Shimosegawa T, Katagiri H.
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Journal Title
Int J Obes (Lond).
Volume: 印刷中
Issue: 9
Pages: 1544-1555
DOI
Related Report
Peer Reviewed / Open Access
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