Switching mechanisms for pancreatic beta-cell growth
| Project/Area Number |
17K08528
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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 |
General physiology
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| Research Institution | Gunma University |
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Principal Investigator |
TORII SEIJI 群馬大学, 食健康科学教育研究センター, 教授 (40312904)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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 | インスリン / 分泌顆粒 / 増殖シグナル / オートクライン / チロシンホスファターゼ / 脱リン酸化酵素 / 膵島細胞 / 糖尿病 |
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| Outline of Final Research Achievements |
Phogrin is a transmembrane protein that localizes on secretory granules in pancreatic β-cells. We previously showed that phogrin participates in molecular interactions with insulin receptors (IR) to regulate insulin receptor substrate 2 (IRS2) protein stability and in turn glucose-promoted β-cell growth. Glucose is a principal regulator of β-cell survival and growth as well as insulin secretion. Despite the growing evidence for the significance of the IR/IRS2-mediated signaling pathways in β-cells, whether secreted insulin acts in an autocrine fashion remains controversial. We showed that phogrin-deficient mice fed a fat diet have defects in β-cell compensatory growth. This is likely because phogrin binds to IR only at conditions that are needed for β-cell expansion. We identified a new phogrin partner, and its binding of phogrin inhibits phogrin-IR interactions. This study represents the first report of a switching regulator of autocrine insulin action in pancreatic β-cells.
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| Academic Significance and Societal Importance of the Research Achievements |
膵β細胞は自身が置かれた状況に応じて、分泌インスリンによるオートクライン増殖を行っていることが明確になった。この成果はβ細胞マスの低下が一因である2型糖尿病の予測、そして新たな予防・治療法の開発につながる。
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Report
(5 results)
Research Products
(35 results)
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[Journal Article] Impaired processing of prohormones in secretogranin III null mice causes maladaptation to an inadequate diet and stress.2018
Author(s)
Yoshinori Maeda, Saki Kudo, Ken Tsushima, Eri Sato, Chisato Kubota, Aika Kayamori, Hiroki Bochimoto, Daisuke Koga, Seiji Torii, Hiroshi Gomi, Tsuyoshi Watanabe, Masahiro Hosaka
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Journal Title
Endocrinology
Volume: 159
Issue: 2
Pages: 1213-1227
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] ATAT1 is essential for regulation of homeostasis-retaining cellular responses in corticotrophs along hypothalamic-pituitary-adrenal axis.2017
Author(s)
Nakakura T, Suzuki T, Torii S, Asano-Hoshino A, Nekooki-Machida Y, Tanaka H, Arisawa K, Nishijima Y, Susa T, Okazaki T, Kiuchi Y, Hagiwara H.
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Journal Title
Cell Tissue Res
Volume: 370
Issue: 1
Pages: 169-178
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] ALOXによる酸化ストレス抵抗性制御2020
Author(s)
富田 和男, 桑原 義和, 鳥居 征司, 五十嵐 健人, 髙 裕子, 長澤 大成, 田中 康一, 北中 純一, 北中 順惠, 栗政 明弘, 西谷 佳5, 西山 信好, 竹村 基彦, 佐藤 友昭
Organizer
第73回日本薬理学会西南部会
Related Report
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