G-protein-coupled receptor 40 agonist GW9508 potentiates glucose-stimulated insulin secretion through activation of protein kinase Cα and ε in INS-1 cells 9

• Material Type: 博士論文
• ISSN: 1932-6203
• Title: G-protein-coupled receptor 40 agonist GW9508 potentiates glucose-stimulated insulin secretion through activation of protein kinase Cα and ε in INS-1 cells
• Volume: 14 9
• Author/Editor: 橋本, 卓也
• Author Heading: 橋本, 卓也
• Publication, Distribution, etc.: PLoS (Public Library of Science)
• Publication Date: 2019-09-09
• Publication Date (W3CDTF): 2019-09-09
• Alternative Title: 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
• Periodical title: PloS one
• Degree grantor/type: 浜松医科大学
• Date Granted: 2020-02-13
• Date Granted (W3CDTF): 2020-02-13
• Dissertation Number: 甲第822号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第822号
• Text Language Code: eng
• Target Audience: 一般
• Note (General): doctoral; 医学系研究科; 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.
• DOI: info:doi/10.1371/journal.pone.0222179; https://doi.org/info:doi/10.1371/journal.pone.0222179
• Persistent ID (NDL): info:ndljp/pid/11498572; https://dl.ndl.go.jp/pid/11498572
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2020-06-07T00:39:19+09:00
• Date Created (W3CDTF): 2020-04-28
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10271/00003719; https://hama-med.repo.nii.ac.jp/records/3587
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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2023-12-09 再収集