Exposure to perfluorooctane sulfonate reduced cell viability and insulin release capacity of β cells.
Exposure to perfluorooctane sulfonate reduced cell viability and insulin release capacity of β cells.
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DOI：
10.1016/j.jes.2021.07.004
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发表时间：
2022
影响因子：
6.9
通讯作者：
W. Qin;Xiaomin Ren;Lixia Zhao;Lianghong Guo
中科院分区：
文献类型：
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作者：
W. Qin;Xiaomin Ren;Lixia Zhao;Lianghong Guo
全氟烷基和多氟烷基物质（PFAS）被发现对人类健康有多种不良后果。最近，流行病学和毒理学研究表明，PFAS暴露对胰腺有不良影响，并与胰岛素异常有关。为了探讨PFAS对糖尿病的影响，我们采用体内和体外方法研究了全氟辛烷磺酸（PFOS）对胰腺β细胞活力和胰岛素释放能力的影响。我们发现给药28天（10mg /（kg体重•天））的全氟辛烷磺酸导致雄性小鼠胰腺重量和胰岛大小减少。全氟辛烷磺酸也导致雄性小鼠空腹和葡萄糖输注后血清胰岛素水平降低。对于细胞为基础的微生物测定，我们使用小鼠β-TC-6癌细胞，发现暴露于50 μmol/L的PFOS 48小时降低了细胞活力。通过对上清中胰岛素含量的测定，PFOS （100 μmol/L）预处理48小时可降低葡萄糖刺激后β-TC-6细胞的胰岛素释放能力。虽然这些浓度高于全氟辛烷磺酸的环境浓度，但考虑到小鼠对全氟辛烷磺酸的去除效率比人快，高浓度全氟辛烷磺酸对小鼠产生可观察到的毒性作用可能是合理的。PFOS （50 μmol/L）暴露于β-TC-6细胞可诱导细胞内活性氧（ROS）积累。过量的活性氧诱导细胞的反应性毒性，最终引起细胞凋亡和坏死。本研究结果为全氟辛烷磺酸暴露与糖尿病风险之间可能存在的因果关系提供了证据。
Per- and polyfluoroalkyl substances (PFAS) are found to have multiple adverse outcomes on human health. Recently, epidemiological and toxicological studies showed that exposure to PFAS had adverse impacts on pancreas and showed association with insulin abnormalities. To explore how PFAS may contribute to diabetes, we studied impacts of perfluorooctane sulfonate (PFOS) on cell viability and insulin release capacity of pancreatic β cells by usingin vivoandin vitromethods. We found that 28-day administration with PFOS (10 mg/(kg body weight•day)) caused reductions of pancreas weight and islet size in male mice. PFOS administration also led to lower serum insulin level both in fasting state and after glucose infusion among male mice. For cell-basedin vitrobioassay, we used mouse β-TC-6 cancer cells and found 48-hr exposure to PFOS decreased the cell viability at 50 μmol/L. By measuring insulin content in supernatant, 48-hr pretreatment of PFOS (100 μmol/L) decreased the insulin release capacity of β-TC-6 cells after glucose stimulation. Although these concentrations were higher than the environmental concentration of PFOS, it might be reasonable for high concentration of PFOS to exert observable toxic effects in mice considering mice had a faster removal efficiency of PFOS than human. PFOS exposure (50 μmol/L) to β-TC-6 cells induced intracellular accumulation of reactive oxidative specie (ROS). Excessive ROS induced the reactive toxicity of cells, which eventually invoke apoptosis and necrosis. Results in this study provide evidence for the possible causal link of exposure to PFOS and diabetes risk.