2023 Fiscal Year Final Research Report
Functional analysis of a novel membrane protein involved in the quality control of insulin in pancreatic beta cells
| Project/Area Number |
21K06856
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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 49010:Pathological biochemistry-related
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
田代 文 大阪大学, 大学院医学系研究科, 助教 (40136213)
宮崎 早月 大阪大学, 大学院医学系研究科, 助教 (60452439)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 糖尿病 / インスリン分泌 / 膵β細胞 / ノックアウトマウス / インスリンプロセッシング / 耐糖能異常 |
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| Outline of Final Research Achievements |
Using the pancreatic β cell line MIN6, Tmem59l was identified as a candidate gene involved in the regulation of insulin secretion. To analyze the function of TMEM59L, knockout (KO) mice were generated, and their detailed analyses were performed. TMEM59L was localized to the Golgi apparatus and secretory granules of β cells. KO mice had no abnormal appearance, but after 15 weeks of age, weight gain in males was lower than in heterozygous mice. When an oral glucose tolerance test was performed on KO male mice, decreased glucose tolerance was observed at 50 weeks of age. To analyze Tmem59l function, we established a Tmem59l KO β cell line and its rescue cell line. Electron microscopy showed that the number of insulin secretory granules and their electron density tended to be lower in KO cells, and insulin secretion was also lower in KO cells than in rescue cells when exposed to high glucose.
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| Free Research Field |
糖尿病学
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病は生活習慣の変化に伴い増加している。糖尿病の抜本的な治療のためにもインスリンを産生・分泌する膵β細胞の機能、特にグルコース応答性インスリン分泌 (GSIS)の低下に影響する遺伝子に関する研究が重要である。GSISの低下に相関して発現が低下する遺伝子群を研究代表者らのグループで独自に探索し見出したTmem59l遺伝子に関し、本研究でノックアウトマウス、ノックアウト膵β細胞株MIN6を用いて、詳細な機能解析を行った。その結果、TMEM59L蛋白が、ゴルジ装置、インスリン分泌顆粒に局在し、インスリン分泌制御で重要な役割を果たしていることが示された。今後、糖尿病発症機構との関連が注目される、
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