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ID 116761
タイトル別表記
Discovery of an endoplasmic reticulum proteostasis modulator that enhances insulin production in pancreatic β cells
著者
Sobajima, Mitsuaki Tokushima University
重永, 章 Tokushima University|Fukuyama University KAKEN研究者をさがす
Sakane, Naoki JT
キーワード
ER stress
unfolded protein response
pancreatic β cell
insulin
chemical chaperone
BiP
資料タイプ
学術雑誌論文
抄録
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.
掲載誌名
Cell Chemical Biology
ISSN
24519456
出版者
Elsevier
29
6
開始ページ
996
終了ページ
1009.e9
発行日
2022-02-09
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/
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
著者版
部局
先端酵素学研究所
病院
薬学系