Elucidation of the mechanism of pancreatic alfa cell mass increase and white adipocyte browning induced by a low-carbohydrate/high-protein diet
| Project/Area Number |
18K08516
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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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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | Yamaguchi University |
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Principal Investigator |
Okuya Shigeru 山口大学, 教育・学生支援機構, 教授 (20214083)
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| Co-Investigator(Kenkyū-buntansha) |
田部 勝也 山口大学, 医学部附属病院, 講師 (00397994)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | グルカゴン / 膵α細胞 / 低炭水化物 / 高蛋白質 / 新生 / 高蛋白 / 褐色脂肪細胞 |
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| Outline of Final Research Achievements |
It is unclear how pancreatic endocrine cells behave in response to nutritional changes. When mice were loaded with a low-carbohydrate/high-protein diet (LC/HP diet) for 1 to 2 weeks, there was no significant difference in blood glucose levels compared to the control diet group. But, it was confirmed that (1) decrease of hepatic glycogen content, (2) increased blood glucagon and decreased insulin, (3) increase of pancreatic glucagon-positive α cell volume, and (4) increment of α cell mass mainly around the pancreatic duct and α cell appearance around the pancreatic islets in the vicinity. Furthermore, (5) hepatic afferent vagotomy and pancreatic sympathetic neuropharmacological blockade completely suppressed the appearance of α cell population and increase in cell mass. Therefore, it was found that there is a new control mechanism of pancreatic α cell mass via a neural network originating from the liver.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の我々の研究により、比較的短期間のLC/HP食で誘導される、代謝臓器である肝臓を起点とする神経ネットワークを介した新たな膵α細胞量制御機構が存在することが判明した。さらに、膵管近傍細胞から分化・新生したα細胞は、交感神経系を介したα細胞新生・増殖であり、この様な報告は未だされておらず、これは“膵α細胞量の調節機構”を解明する上で貴重なモデルと考えられる。さらに、膵管結紮モデルでの観察より膵幹細胞は傍膵管のfocal areaに存在するといわれており、我々の観察はそれを裏付けている可能性がある。このモデルを解析することで、自律神経を介した新たな膵内分泌機能制御の解明が期待される。
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Islet cell dedifferentiation is a pathologic mechanism of long-standing progression of type 2 diabetes.2021
Author(s)
Amo-Shiinoki K, Tanabe K, Hoshii Y, Matsui H, Harano R, Fukuda T, Takeuchi T, Bouchi R, Takagi T, Hatanaka M, Takeda K, Okuya S, Nishimura W, Kudo A, Tanaka S, Tanabe M, Akashi T, Yamada T, Ogawa Y, Ikeda E, Nagano H, Tanizawa Y.
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Journal Title
JCI Insight
Volume: 6
Issue: 1
Pages: 143791-143791
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Importance of Intestinal Environment and Cellular Plasticity of Islets in the Development of Postpancreatectomy Diabetes.2021
Author(s)
Fukuda T, Bouchi R, Takeuchi T, Amo-Shiinoki K, Kudo A, Tanaka S, Tanabe M, Akashi T, Hirayama K, Odamaki T, Igarashi M, Kimura I, Tanabe K, Tanizawa Y, Yamada T, Ogawa Y
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Journal Title
Diabetes Care
Volume: 44(4)
Issue: 4
Pages: 1002-1011
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] 時計遺伝子E4BP4/DBPの膵β細胞における役割の解明.2018
Author(s)
田口昭彦, 太田康晴, 松村卓郎, 中林容子, 秋山 優, 山本 薫, 藤本留理子, 末冨吏佐, 柳井章江, 篠田 晃, 奥屋 茂, 谷澤幸生
Organizer
日本糖尿病学会中国四国地方会第56回総会
Related Report
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