神戸大学附属図書館デジタルアーカイブ
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https://hdl.handle.net/20.500.14094/90005255
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2024-04-26
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90005255 (fulltext)
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メタデータID
90005255
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open access
出版タイプ
Version of Record
タイトル
PHD3 regulates glucose metabolism by suppressing stress-induced signalling and optimising gluconeogenesis and insulin signalling in hepatocytes
著者
Yano, Hiroyuki ; Sakai, Mashito ; Matsukawa, Toshiya ; Yagi, Takashi ; Naganuma, Takao ; Mitsushima, Masaru ; Iida, Satoshi ; Inaba, Yuka ; Inoue, Hiroshi ; Unoki-Kubota, Hiroyuki ; Kaburagi, Yasushi ; Asahara, Shun-ichiro ; Kido, Yoshiaki ; Minami, Shiro ; Kasuga, Masato ; Matsumoto, Michihiro
著者名
Yano, Hiroyuki
著者名
Sakai, Mashito
著者名
Matsukawa, Toshiya
著者名
Yagi, Takashi
著者名
Naganuma, Takao
著者名
Mitsushima, Masaru
著者名
Iida, Satoshi
著者名
Inaba, Yuka
著者名
Inoue, Hiroshi
著者名
Unoki-Kubota, Hiroyuki
著者名
Kaburagi, Yasushi
著者ID
A1964
研究者ID
1000000570342
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=9aa517d3d9280b80520e17560c007669
著者名
Asahara, Shun-ichiro
淺原, 俊一郎
アサハラ, シュンイチロウ
所属機関名
医学部附属病院
著者ID
A0779
研究者ID
1000010335440
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=cce27e71728d2870520e17560c007669
著者名
Kido, Yoshiaki
木戸, 良明
キド, ヨシアキ
所属機関名
保健学研究科
著者名
Minami, Shiro
著者名
Kasuga, Masato
著者名
Matsumoto, Michihiro
収録物名
Scientific Reports
巻(号)
8
ページ
14290-14290
出版者
Springer Nature
刊行日
2018-09-24
公開日
2018-10-09
抄録
Glucagon-mediated gene transcription in the liver is critical for maintaining glucose homeostasis. Promoting the induction of gluconeogenic genes and blocking that of insulin receptor substrate (Irs)2 in hepatocytes contributes to the pathogenesis of type 2 diabetes. However, the molecular mechanism by which glucagon signalling regulates hepatocyte metabolism is not fully understood. We previously showed that a fasting-inducible signalling module consisting of general control non-repressed protein 5, co-regulator cAMP response element-binding protein binding protein/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2, and protein kinase A is required for glucagon-induced transcription of gluconeogenic genes. The present study aimed to identify the downstream effectors of this module in hepatocytes by examining glucagon-induced potential target genes. One of these genes was prolyl hydroxylase domain (PHD)3, which suppressed stress signalling through inhibition of the IκB kinase–nuclear factor-κB pathway in a proline hydroxylase-independent manner to maintain insulin signalling. PHD3 was also required for peroxisome proliferator–activated receptor γ coactivator 1α-induced gluconeogenesis, which was dependent on proline hydroxylase activity, suggesting that PHD3 regulates metabolism in response to glucagon as well as insulin. These findings demonstrate that glucagon-inducible PHD3 regulates glucose metabolism by suppressing stress signalling and optimising gluconeogenesis and insulin signalling in hepatocytes.
カテゴリ
医学部附属病院
保健学研究科
学術雑誌論文
権利
© The Author(s) 2018.
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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資源タイプ
journal article
言語
English (英語)
eISSN
2045-2322
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関連情報
DOI
https://doi.org/10.1038/s41598-018-32575-z
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