ID | 116761 |
タイトル別表記 | Discovery of an endoplasmic reticulum proteostasis modulator that enhances insulin production in pancreatic β cells
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著者 |
Sobajima, Mitsuaki
Tokushima University
Sakane, Naoki
JT
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キーワード | ER stress
unfolded protein response
pancreatic β cell
insulin
chemical chaperone
BiP
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資料タイプ |
学術雑誌論文
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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.
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掲載誌名 |
Cell Chemical Biology
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ISSN | 24519456
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出版者 | Elsevier
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巻 | 29
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号 | 6
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開始ページ | 996
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終了ページ | 1009.e9
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発行日 | 2022-02-09
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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/
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言語 |
eng
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著者版フラグ |
著者版
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部局 |
先端酵素学研究所
病院
薬学系
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