Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme, Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada.
Front Endocrinol (Lausanne). 2024 Aug 22;15:1422279. doi: 10.3389/fendo.2024.1422279. eCollection 2024.
Type 1 Diabetes (T1D) is a chronic metabolic disease resulting from insulin deficiency due to autoimmune loss of pancreatic β cells. In addition to β cell destruction, it is now accepted that β cell stress and dysfunction, such as senescence, plays a crucial role in the development of the disease. Accumulation of senescent β cells occurs during development of T1D in humans and contributes to the progression of T1D in the nonobese diabetic (NOD) mouse model. Senescent β cells are thought to exacerbate the inflammatory response within the islets by production and secretion of senescence-associated secretory phenotype (SASP). Extracellular vesicles (EVs) from β cells have been shown to carry protein and microRNAs (miRNAs), influencing cellular signaling and may contribute to the development of T1D but it remains to be addressed how senescence impacts β cell EV cargo. In this minireview, we discuss emerging evidence that EV cargo proteins and miRNAs associated with senescence could contribute to the development of T1D and could suggest potential biomarkers and therapeutic targets for the regulation of SASP and elimination of senescent β cells in T1D. Future investigation exploring the intricate relationship between β cell senescence, EVs and miRNAs could pave the way for the development of novel diagnostic techniques and therapeutic interventions.
1 型糖尿病（T1D）是一种慢性代谢性疾病，由于自身免疫导致胰岛β细胞丧失而引起胰岛素缺乏。除了β细胞破坏，现在人们接受β细胞应激和功能障碍（如衰老）在疾病的发展中起着关键作用。衰老β细胞在人类 T1D 的发展过程中积累，并导致非肥胖型糖尿病（NOD）小鼠模型中 T1D 的进展。衰老β细胞被认为通过产生和分泌衰老相关分泌表型（SASP）加剧胰岛内的炎症反应。已经表明β细胞来源的细胞外囊泡（EVs）携带蛋白质和 microRNAs（miRNAs），影响细胞信号转导，可能有助于 T1D 的发展，但仍需要解决衰老如何影响β细胞 EV 货物。在这篇小综述中，我们讨论了新出现的证据，即与衰老相关的 EV 货物蛋白和 miRNAs 可能有助于 T1D 的发展，并可能为调节 SASP 和消除 T1D 中的衰老β细胞提供潜在的生物标志物和治疗靶点。未来探索β细胞衰老、EVs 和 miRNAs 之间复杂关系的研究可能为开发新的诊断技术和治疗干预铺平道路。
