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G-protein-coupled receptor 40 agonist GW9508 potentiates glucose-stimulated insulin secretion through activation of protein kinase Cα and ε in INS-1 cells
http://hdl.handle.net/10271/00003719
http://hdl.handle.net/10271/00003719f93959da-fbff-478d-9a78-3c0080f2c929
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
論文本文 (1.7 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2020-04-28 | |||||
| タイトル | ||||||
| タイトル | G-protein-coupled receptor 40 agonist GW9508 potentiates glucose-stimulated insulin secretion through activation of protein kinase Cα and ε in INS-1 cells | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
| 資源タイプ | doctoral thesis | |||||
| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| その他のタイトル | ||||||
| その他のタイトル | Gタンパク質共益型受容体40作動薬であるGW9508はINS-1細胞においてプロテインキナーゼ Cα および ε の活性化を介してグルコース刺激性インスリン分泌を増強する | |||||
| 言語 | ja | |||||
| 著者 |
橋本, 卓也
× 橋本, 卓也 |
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| 書誌情報 |
en : PloS one 巻 14, 号 9, p. e0222179, 発行日 2019-09-09 |
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| 出版者 | ||||||
| 出版者 | PLoS (Public Library of Science) | |||||
| 言語 | en | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objective: The mechanism by which G-protein-coupled receptor 40 (GPR40) signaling amplifies glucose-stimulated insulin secretion through activation of protein kinase C (PKC) is unknown. We examined whether a GPR40 agonist, GW9508, could stimulate conventional and novel isoforms of PKC at two glucose concentrations (3mM and 20mM) in INS-1D cells. Methods: Using epifluorescence microscopy, we monitored relative changes in the cytosolic fluorescence intensity of Fura2 as a marker of change in intracellular Ca2+([Ca2+]i) and relative increases in green fluorescent protein (GFP)-tagged myristoylated alanine-rich C kinase substrate (MARCKS-GFP) as a marker of PKC activation in response to GW9508 at 3mM and 20mM glucose. To assess the activation of the two PKC isoforms, relative increases in membrane fluorescence intensity of PKCα-GFP and PKCε-GFP were measured by total internal reflection fluorescence microscopy. Specific inhibitors of each PKC isotype were constructed and synthesized as peptide fusions with the third α-helix of the homeodomain of Antennapedia. Results: At 3mM glucose, GW9508 induced sustained MARCKS-GFP translocation to the cytosol, irrespective of changes in [Ca2+]i. At 20mM glucose, GW9508 induced sustained MARCKS-GFP translocation but also transient translocation that followed sharp increases in [Ca2+]i. Although PKCα translocation was rarely observed, PKCε translocation to the plasma membrane was sustained by GW9508 at 3mM glucose. At 20mM glucose, GW9508 induced transient translocation of PKCα and sustained translocation as well as transient translocation of PKCε. While the inhibitors (75μM) of each PKC isotype reduced GW9508-potentiated, glucose-stimulated insulin secretion in INS-1D cells, the PKCε inhibitor had a more potent effect. Conclusion: GW9508 activated PKCε but not PKCα at a substimulatory concentration of glucose. Both PKC isotypes were activated at a stimulatory concentration of glucose and contributed to glucose-stimulated insulin secretion in insulin-producing cells. |
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| 言語 | en | |||||
| 学位名 | ||||||
| 言語 | ja | |||||
| 学位名 | 博士（医学） | |||||
| 学位の区分 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | doctoral | |||||
| 言語 | en | |||||
| 学位の分野 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 医学系研究科 | |||||
| 言語 | ja | |||||
| 学位授与機関 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 13802 | |||||
| 言語 | ja | |||||
| 学位授与機関名 | 浜松医科大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2020-02-13 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲第822号 | |||||
| EISSN | ||||||
| 収録物識別子タイプ | EISSN | |||||
| 収録物識別子 | 1932-6203 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 31498851 | |||||
| 出版社DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1371/journal.pone.0222179 | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
