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/20.500.14094/90004234
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2024-04-26
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90004234 (fulltext)
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メタデータID
90004234
アクセス権
open access
出版タイプ
Version of Record
タイトル
Histone deacetylase regulates insulin signaling via two pathways in pancreatic β cells
著者
Kawada, Yukina ; Asahara, Shun-ichiro ; Sugiura, Yumiko ; Sato, Ayaka ; Furubayashi, Ayuko ; Kawamura, Mao ; Bartolome, Alberto ; Terashi-Suzuki, Emi ; Takai, Tomoko ; Kanno, Ayumi ; Koyanagi-Kimura, Maki ; Matsuda, Tomokazu ; Hashimoto, Naoko ; Kido, Yoshiaki
著者名
Kawada, Yukina
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
著者名
Sugiura, Yumiko
著者名
Sato, Ayaka
著者名
Furubayashi, Ayuko
著者名
Kawamura, Mao
著者名
Bartolome, Alberto
著者名
Terashi-Suzuki, Emi
著者名
Takai, Tomoko
著者名
Kanno, Ayumi
著者名
Koyanagi-Kimura, Maki
著者名
Matsuda, Tomokazu
著者名
Hashimoto, Naoko
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
収録物名
PLoS ONE
巻(号)
12(9)
ページ
e0184435-e0184435
出版者
Public Library of Science
刊行日
2017-09-08
公開日
2017-10-12
抄録
Recent studies demonstrated that insulin signaling plays important roles in the regulation of pancreatic β cell mass, the reduction of which is known to be involved in the development of diabetes. However, the mechanism underlying the alteration of insulin signaling in pancreatic β cells remains unclear. The involvement of epigenetic control in the onset of diabetes has also been reported. Thus, we analyzed the epigenetic control of insulin receptor substrate 2 (IRS2) expression in the MIN6 mouse insulinoma cell line. We found concomitant IRS2 up-regulation and enhanced insulin signaling in MIN6 cells, which resulted in an increase in cell proliferation. The H3K9 acetylation status of the Irs2 promoter was positively associated with IRS2 expression. Treatment of MIN6 cells with histone deacetylase inhibitors led to increased IRS2 expression, but this occurred in concert with low insulin signaling. We observed increased IRS2 lysine acetylation as a consequence of histone deacetylase inhibition, a modification that was coupled with a decrease in IRS2 tyrosine phosphorylation. These results suggest that insulin signaling in pancreatic β cells is regulated by histone deacetylases through two novel pathways affecting IRS2: the epigenetic control of IRS2 expression by H3K9 promoter acetylation, and the regulation of IRS2 activity through protein modification. The identification of the histone deacetylase isoform(s) involved in these mechanisms would be a valuable approach for the treatment of type 2 diabetes.
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
© 2017 Kawada et al.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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資源タイプ
journal article
言語
English (英語)
eISSN
1932-6203
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関連情報
DOI
https://doi.org/10.1371/journal.pone.0184435
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