He Zhaxicao, Liu Qian, Wang Yan, Zhao Bing, Zhang Lumei, Yang Xia, Wang Zhigang
Gansu University of Chinese Medicine, Lanzhou, China.
Tianshui Hospital of Traditional Chinese Medicine, Tianshui, China.
PeerJ. 2025 Mar 28;13:e19192. doi: 10.7717/peerj.19192. eCollection 2025.
Type 2 diabetes mellitus (T2DM) is a globally prevalent metabolic disorder characterized by insulin resistance and dysfunction of islet cells. Endoplasmic reticulum (ER) stress plays a crucial role in the pathogenesis and progression of T2DM, especially in the function and survival of β-cells. β-cells are particularly sensitive to ER stress because they require substantial insulin synthesis and secretion energy. In the early stages of T2DM, the increased demand for insulin exacerbates β-cell ER stress. Although the unfolded protein response (UPR) can temporarily alleviate this stress, prolonged or excessive stress leads to pancreatic cell dysfunction and apoptosis, resulting in insufficient insulin secretion. This review explores the mechanisms of ER stress in T2DM, particularly its impact on islet cells. We discuss how ER stress activates UPR signaling pathways to regulate protein folding and degradation, but when stress becomes excessive, these pathways may contribute to β-cell death. A deeper understanding of how ER stress impacts islet cells could lead to the development of novel T2DM treatment strategies aimed at improving islet function and slowing disease progression.
2型糖尿病（T2DM）是一种全球流行的代谢紊乱疾病，其特征为胰岛素抵抗和胰岛细胞功能障碍。内质网（ER）应激在T2DM的发病机制和进展中起着关键作用，尤其是在β细胞的功能和存活方面。β细胞对ER应激特别敏感，因为它们需要大量能量用于胰岛素的合成和分泌。在T2DM的早期阶段，对胰岛素需求的增加加剧了β细胞的ER应激。尽管未折叠蛋白反应（UPR）可以暂时缓解这种应激，但长期或过度的应激会导致胰腺细胞功能障碍和凋亡，从而导致胰岛素分泌不足。本综述探讨了T2DM中ER应激的机制，特别是其对胰岛细胞的影响。我们讨论了ER应激如何激活UPR信号通路来调节蛋白质折叠和降解，但当应激过度时，这些通路可能导致β细胞死亡。深入了解ER应激如何影响胰岛细胞可能会促使开发旨在改善胰岛功能和减缓疾病进展的新型T2DM治疗策略。
