Lei Lichao, Chen Mengling, Qin Chuan, Cai Linli, Liang Bing
School of Basic Medicine, Guizhou Medical University, Guian New District, 561113, Guizhou, China.
School of Basic Medicine, Guizhou Medical University, Guian New District, 561113, Guizhou, China; The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guian New District, 561113, Guizhou, China.
Chem Biol Interact. 2025 Jan 25;406:111348. doi: 10.1016/j.cbi.2024.111348. Epub 2024 Dec 13.
The relationship between arsenic exposure and the development of diabetes mellitus has garnered significant interest in recent years. However, current experimental studies have not definitively established the role of arsenic in the onset of diabetes mellitus. To investigate this relationship specifically concerning type 1 diabetes mellitus, Streptozocin (STZ) was utilized as an inducer to initiate the fundamental pathological changes associated with the disease. A high dose of STZ (50 mg/kg) served as the positive control, while a low dose of STZ (20 mg/kg) was administered in combination with arsenic at varying doses. The objective was to determine whether arsenic enhances the effects of STZ, thereby leading to an expedited onset and progression of type 1 diabetes mellitus. The preliminary investigation into the impact of arsenic exposure on experimental type 1 diabetic mice focused on the NLRP3/Caspase-1/GSDMD mediated pyroptosis pathway. The results showed that fasting blood glucose (FBG) was increased, glucose tolerance was impaired, insulin sensitivity was decreased, fasting serum insulin and the homeostatic model assessment-β (HOMA-β) were significantly reduced, hair arsenic content was increased, reactive oxygen species(ROS), interleukin (IL)-1β and IL-18 contents were increased, and the pathological morphology of pancreas was more serious in the combined group. Moreover, the expression levels of proteins associated with the NLRP3/Caspase-1/GSDMD-mediated pyroptosis pathway were elevated in the combined group. This study illustrates that exposure to arsenic, combined with low-dose STZ, not only leads to pancreatic injury in mice, impacting insulin secretion and causing elevated blood glucose levels, thereby hastening the progression of type 1 diabetes, but also induces pyroptosis in pancreatic tissues by influencing the NLRP3/Caspase-1/GSDMD signaling pathway, further facilitating the development of type 1 diabetes.
近年来，砷暴露与糖尿病发生之间的关系引起了广泛关注。然而，目前的实验研究尚未明确砷在糖尿病发病中的作用。为了具体研究这种与1型糖尿病相关的关系，使用链脲佐菌素（STZ）作为诱导剂引发与该疾病相关的基本病理变化。高剂量的STZ（50mg/kg）作为阳性对照，而低剂量的STZ（20mg/kg）与不同剂量的砷联合给药。目的是确定砷是否会增强STZ的作用，从而导致1型糖尿病的发病和进展加快。对砷暴露对实验性1型糖尿病小鼠影响的初步研究集中在NLRP3/Caspase-1/GSDMD介导的焦亡途径上。结果表明，联合组空腹血糖（FBG）升高、糖耐量受损、胰岛素敏感性降低、空腹血清胰岛素和稳态模型评估-β（HOMA-β）显著降低、毛发砷含量增加、活性氧（ROS）、白细胞介素（IL）-1β和IL-18含量增加，胰腺病理形态更严重。此外，联合组中与NLRP3/Caspase-1/GSDMD介导的焦亡途径相关的蛋白质表达水平升高。本研究表明砷暴露与低剂量STZ联合不仅导致小鼠胰腺损伤，影响胰岛素分泌并导致血糖水平升高，从而加速1型糖尿病的进展，还通过影响NLRP3/Caspase-1/GSDMD信号通路诱导胰腺组织焦亡，进一步促进1型糖尿病的发展。
