文献类型：期刊文献

英文题名：Coupled endoplasmic reticulum and oxidative stress in pancreatic β cells: mechanisms and therapeutic insights

作者：He, Zhaxicao[1];Liu, Qian[1];Yue, Xiaohua[1];Zhao, Heng[1];Yu, Jiaorong[1];Zhang, Lumei[1];Wang, Yan[1];Zhao, Bing[1];Yang, Xia[2];Wang, Zhigang[1,2]

第一作者：He, Zhaxicao

通信作者：Wang, ZG[1];Wang, ZG[2];Yang, X[2]

机构：[1]Gansu Univ Chinese Med, Sch Clin Chinese Med, Lanzhou, Peoples R China;[2]Gansu Univ Chinese Med, Tianshui Hosp Tradit Chinese Med, TCM Internal Med, Tianshui, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Sch Clin Chinese Med, Lanzhou, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Tianshui Hosp Tradit Chinese Med, TCM Internal Med, Tianshui, Peoples R China.|[10735]甘肃中医药大学;

年份：2026

卷号：14

起止页码：1

外文期刊名：PEERJ

收录：;Scopus(收录号：2-s2.0-105037807126);WOS:【SCI-EXPANDED(收录号:WOS:001739141600001)】；

基金：This work was supported by the Natural Science Foundation of Gansu Province (25JRRE013), Subject of Gansu Provincial Administration of Chinese Medicine (GZKZ-2024-39). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

语种：英文

外文关键词：Pancreatic beta cells; Endoplasmic reticulum stress; Oxidative stress; Redox homeostasis

摘要：Pancreatic beta cells maintain glycemic homeostasis through high-rate insulin synthesis and secretion, and their function depends on precise protein folding and the redox microenvironment. In diabetes, inflammation, chronic hyperglycemia, and lipotoxicity disrupt redox homeostasis, with increased reactive oxygen species and compromised antioxidant defenses that directly reduce secretory efficiency and endanger cell survival. Oxidative stress and endoplasmic reticulum stress are tightly coupled. Excessive oxidative load raises folding demand and chronically activates the unfolded protein response, which further perturbs calcium signaling and redox balance to form a vicious cycle. When endoplasmic reticulum stress shifts from adaptive to injurious outputs, beta cells undergo a decline in the secretory phenotype, dedifferentiation, and apoptosis, leading to loss of beta cell mass and function. As interventions, chemical chaperones and antioxidant strategies can jointly lower ER and oxidative burdens and improve islet function. Tauroursodeoxycholic acid and 4-phenylbutyric acid increase folding capacity and improve metabolic phenotypes across models. Overall, combination approaches centered on folding quality control and redox balance hold translational promise, yet optimal dose and timing, long-term safety, and compatibility with existing glucose-lowering therapies remain to be defined. This review summarizes these mechanistic links and therapeutic advances and discusses key challenges and prospects.