Mechanism of pancreatic beta-cell proliferation regulated by nervous system
| Project/Area Number |
16K09762
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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 | Yokohama City University |
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Principal Investigator |
Ito Yuzuru 横浜市立大学, 医学部, 講師 (00512980)
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| Co-Investigator(Kenkyū-buntansha) |
寺内 康夫 横浜市立大学, 医学研究科, 教授 (40359609)
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| Project Period (FY) |
2016-04-01 – 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 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 膵β細胞 / アセチルコリン / GLP-１ / 副交感神経 / インスリン / 糖尿病 |
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| Outline of Final Research Achievements |
This study investigated the role of muscarinic agonists or acetylcholine in regulating the pancreatic β-cell mass and glucose homeostasis. The β-cell mass and proliferation increased following oral administration of bethanechol in wild-type mice. The muscarinic agonists also increased the incorporation of BrdU into islets isolated from wild-type mice and MIN6 cells. In IRS-2 knockout mice, oral administration of the muscarinic agonist did not increase the β-cell mass or proliferation. The phosphorylation of Akt induced by oral administration of bethanechol was observed in wild-type mice, but not in IRS-2 knockout mice. The secretion of GLP-1 was also stimulated by bethanechol in wild-type mice, and the GLP-1 antagonist partially inhibited the bethanechol-induced increase in the β-cell mass. This proliferative effect was dependent on the IRS-2/Akt pathway. The bethanechol-stimulated release of GLP-1 may be indirectly associated with β-cell proliferation.
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| Academic Significance and Societal Importance of the Research Achievements |
ムスカリニックレセプターアゴニストの投与によりマウスでの膵β細胞増殖作用や膵島での血糖依存的なインスリン分泌増強作用を認めることから、新規糖尿病治療薬のターゲットになりえると考えた。in vivoでは、マウスへのbethanechol投与による血糖改善、膵β細胞量増加のモデルを確立し、in vitroでは、マウス単離膵島やMIN6細胞におけるbethanechol刺激によるBrdU取り込みモデルを確立した。こうしたモデルの確立により、アセチルコリンによる膵β細胞への直接的、間接的な作用機序の研究推進が望める。
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Report
(4 results)
Research Products
(7 results)
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[Journal Article] Indicators of the need for insulin treatment and the effect of treatment for gestational diabetes on pregnancy outcomes in Japan2016
Author(s)
Ito Y, Shibuya M, Hosokawa S, Motoki Y, Nagata R, Konishi H, Miyazaki T, Matsunaga T, Nomura Y, Mihara T, Ito S, Sugiura K, Terauchi Y.
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Journal Title
Endocrine Journal
Volume: 63
Issue: 3
Pages: 231-237
DOI
NAID
ISSN
0918-8959, 1348-4540
Related Report
Peer Reviewed / Open Access
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