| アイテムタイプ |
文献 / Documents(1) |
| 公開日 |
2022-03-03 |
| アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 出版社版DOI |
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関連識別子 |
https://doi.org/10.1016/j.chembiol.2022.01.002 |
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関連名称 |
10.1016/j.chembiol.2022.01.002 |
| 出版タイプ |
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出版タイプ |
AM |
|
出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
| タイトル |
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|
タイトル |
Identification of an endoplasmic reticulum proteostasis modulator that enhances insulin production in pancreatic β cells |
| タイトル別表記 |
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その他のタイトル |
Discovery of an endoplasmic reticulum proteostasis modulator that enhances insulin production in pancreatic β cells |
| 著者 |
三宅, 雅人
ソバジマ, ミツアキ
倉橋, 清衛
重永, 章
傳田, 将也
大髙, 章
齋尾, 智英
サカネ, ナオキ
小迫, 英尊
親泊, 政一
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| 抄録 |
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内容記述 |
Perturbation of endoplasmic reticulum (ER) proteostasis is associated with impairment of cellular function in diverse diseases, especially the function of pancreatic β cells in type 2 diabetes. Restoration of ER proteostasis by small molecules thus shows therapeutic promise for type 2 diabetes. Here, we report the discovery of a new chemical chaperone-like small molecule, KM04794, that alleviates ER stress using cell-based screening. KM04794 prevented protein aggregation and cell death caused by ER stressors and a mutant insulin protein. We also found that this compound increased intracellular and secreted insulin levels in pancreatic β cells. Chemical biology and biochemical approaches revealed that the compound accumulated in the ER and directly interacted with the ER molecular chaperone BiP. Our data show that this new corrector of ER proteostasis can enhance insulin storage and pancreatic β cell function. |
| キーワード |
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主題 |
ER stress |
| キーワード |
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主題 |
unfolded protein response |
| キーワード |
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主題 |
pancreatic β cell |
| キーワード |
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主題 |
insulin |
| キーワード |
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|
主題 |
chemical chaperone |
| キーワード |
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主題 |
BiP |
| 書誌情報 |
en : Cell Chemical Biology
巻 29,
号 6,
p. 996-1009.e9,
発行日 2022-02-09
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
24519456 |
| 出版者 |
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出版者 |
Elsevier |
| 権利情報 |
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|
権利情報 |
© 2022. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| EID |
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識別子 |
387398 |
| 言語 |
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言語 |
eng |
chembiol_29_6_996.pdf (1.39 MB)
