2022年6月16日
Identification of an endoplasmic reticulum proteostasis modulator that enhances insulin production in pancreatic β cells
Cell Chemical Biology
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- 巻
- 29
- 号
- 6
- 開始ページ
- 996
- 終了ページ
- 1009
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.chembiol.2022.01.002
- 出版者・発行元
- Elsevier BV
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 shows therapeutic promise for type 2 diabetes. Here, using cell-based screening, we report identification of a chemical chaperone-like small molecule, KM04794, that alleviates ER stress. 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 interacted directly with the ER molecular chaperone BiP. Our data show that this corrector of ER proteostasis can enhance insulin storage and pancreatic β cell function.
- リンク情報
- ID情報
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- DOI : 10.1016/j.chembiol.2022.01.002
- ISSN : 2451-9456
- PubMed ID : 35143772