Department of Immunology, Zanjan University of Medical Sciences, Zanjan, Iran; Cancer Gene Therapy Research Center (CGRC), Zanjan University of Medical Sciences, Zanjan, Iran.
School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
J Diabetes Complications. 2023 Nov;37(11):108564. doi: 10.1016/j.jdiacomp.2023.108564. Epub 2023 Jul 23.
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by sustained hyperglycemia caused by impaired insulin signaling and secretion. Metabolic stress, caused by an inappropriate diet, is one of the major hallmarks provoking inflammation, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction. Heat shock proteins (HSPs) are a group of highly conserved proteins that have a crucial role in chaperoning damaged and misfolded proteins to avoid disruption of cellular homeostasis under stress conditions. To do this, HSPs interact with diverse intra-and extracellular pathways among which are the insulin signaling, insulin secretion, and apoptosis pathways. Therefore, HSP dysfunction, e.g. HSP70, may lead to disruption of the pathways responsible for insulin secretion and uptake. Consistently, the altered expression of other HSPs and genetic polymorphisms in HSP-producing genes in diabetic subjects has made HSPs hot research in T2DM. This paper provides a comprehensive overview of the role of different HSPs in T2DM pathogenesis, affected cellular pathways, and the potential therapeutic strategies targeting HSPs in T2DM.
2 型糖尿病（T2DM）是一种代谢紊乱疾病，其特征为胰岛素信号和分泌受损导致的持续高血糖。代谢应激是引起炎症、内质网（ER）应激和线粒体功能障碍的主要标志之一，其由不适当的饮食引起。热休克蛋白（HSPs）是一组高度保守的蛋白质，在应激条件下对受损和错误折叠的蛋白质进行伴侣介导方面发挥着关键作用，以避免破坏细胞内稳态。为此，HSPs 与多种细胞内和细胞外途径相互作用，其中包括胰岛素信号转导、胰岛素分泌和细胞凋亡途径。因此，HSP 功能障碍（例如 HSP70）可能导致负责胰岛素分泌和摄取的途径中断。一致地，糖尿病患者中 HSP 产生基因的其他 HSP 的改变表达和遗传多态性使得 HSP 成为 T2DM 的热门研究领域。本文全面概述了不同 HSP 在 T2DM 发病机制、受影响的细胞途径以及针对 T2DM 的 HSP 潜在治疗策略中的作用。
