Fate determination of pancreatic beta cells by glucokinase activation
| Project/Area Number |
16H05329
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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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 |
Terauchi Yasuo 横浜市立大学, 医学研究科, 教授 (40359609)
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| Co-Investigator(Kenkyū-buntansha) |
伊藤 譲 横浜市立大学, 医学部, 講師 (00512980)
富樫 優 横浜市立大学, 附属病院, 助教 (10710444)
白川 純 横浜市立大学, 医学部, 助教 (70625532)
田島 一樹 横浜市立大学, 医学研究科, 客員研究員 (00725236)
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| Research Collaborator |
Tajima Kazuki 横浜市立大学, 医学研究科, 客員研究員 (00725236)
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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 |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2016: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Keywords | 膵島 / グルコキナーゼ / 膵β細胞 / S100A8 / 糖尿病 / 糖 |
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| Outline of Final Research Achievements |
We had investigated the impacts of glucokinase-mediated glucose signal in the regulation of beta cell function and proliferation. We now systematically investigated changes in the expression of genes involved in beta cell function and proliferation in mouse islets stimulated with glucokinase activator (GKA). GKA-stimulated IRS2 production affected beta cell proliferation but not beta cell function. Specifically, we focused the roles of fibulin 5, EGFR and S100A8 in beta cells. Of note, both glucotoxicity and lipotoxicity triggered S100A8 secretion from pancreatic islets, which in turn promoted macrophage infiltration of the islets. A positive feedback loop between islet-derived S100A8 and macrophages drives beta-cell apoptosis and pancreatic islet inflammation.
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| Academic Significance and Societal Importance of the Research Achievements |
膵島における糖代謝シグナルはグルコース応答性インスリン分泌に不可欠であるが、糖が溢れた状態ではインスリン分泌が低下することが知られていた。S100A8は高血糖および高遊離脂肪酸により惹起される膵島炎症に関わっていたことから、膵島機能保持の標的としてS100A8が浮上してきた。
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Report
(4 results)
Research Products
(39 results)
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[Journal Article] Signaling between pancreatic beta-cells and macrophages via S100 calcium-binding protein A8 exacerbates beta-cell apoptosis and islet inflammation.2018
Author(s)
Inoue H, Shirakawa J, Togashi Y, Tajima K, Okuyama T, Kyohara M, Tanaka Y, Saisho Y, Yamada T, Shibue K, Kulkarni RN, Terauchi Y
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Journal Title
The Journal of Biological Chemistry
Volume: 293
Issue: 16
Pages: 5934-5946
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Differential hepatic distribution of insulin receptor substrates causes selective insulin resistance in diabetes and obesity.2016
Author(s)
Kubota N, Kubota T, Kajiwara E, Iwamura T, Kumagai H, Watanabe T, Inoue M, Takamoto I, Sasako T, Kumagai K, Kohjima M, Nakamuta M, Moroi M, Sugi K, Noda T, Terauchi Y, Ueki K, Kadowaki T.
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Journal Title
Nat Commun.
Volume: 7
Issue: 1
Pages: 12977-12977
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Pioglitazone Ameliorates Smooth Muscle Cell Proliferation in Cuff-Induced Neointimal Formation by Both Adiponectin-Dependent and -Independent Pathways.2016
Author(s)
Kubota T, Kubota N, Sato H, Inoue M, Kumagai H, Iwamura T, Takamoto I, Kobayashi T, Moroi M, Terauchi Y, Tobe K, Ueki K, Kadowaki T
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Journal Title
Sci Rep
Volume: 6
Issue: 1
Pages: 34707-34707
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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