2020 Fiscal Year Final Research Report
Analysis of insulin secretory function in syndecan-4 knockout mice
| Project/Area Number |
18K06919
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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 48040:Medical biochemistry-related
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| Research Institution | Iwate Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山田 修平 名城大学, 薬学部, 教授 (70240017)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | ヘパラン硫酸プロテオグリカン / コアタンパク質Syndecan-4 / インスリン分泌 / 膵β細胞 / 糖尿病 |
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| Outline of Final Research Achievements |
Syndecane-4 (SDC4) is one of the core proteins that compose heparan sulfate proteoglycans and has been reported to be involved in glucose-induced insulin secretion (GIS) in cultured cell lines. Analysis of GIS function using SDC4 knockout (KO) mice revealed that C57BL/6J (B6) strain-derived SDC4KO mice exhibited GIS disorders, but no abnormalities were observed in the ICR strain-derived SDC4KO mice. Investigation of the effects of SDC4 in an ICR strain-derived mouse model of slowly progressive diabetes induced using low doses of STZ showed markedly higher casual blood glucose levels and lower casual insulin secretion values in SDC4KO mice than in controls. These results indicate that SDC4 is involved in GIS function of β-cells not only in cultured cells but also in living mice, although there are differences among strains.
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| Free Research Field |
分子生物学、生化学、糖鎖生物学
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| Academic Significance and Societal Importance of the Research Achievements |
膵β細胞におけるインスリン分泌機能にシンデカン4(SDC4)が関与することが、マウス培養細胞実験系のみならずマウス生体内でも明らかとなった。SDC4ノックアウトマウスを用いた研究報告は複数あるが、インスリン分泌機能を詳細に解析した報告は本研究報告が初めてである。本研究により、SDC4が糖尿病の病態解明や治療のための新しい標的分子となる可能性が高まった。
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