State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Center for Eco-environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
Institute of Environmental and Health Sciences, China Jiliang University, Hangzhou 310018, China.
J Environ Sci (China). 2022 May;115:162-172. doi: 10.1016/j.jes.2021.07.004. Epub 2021 Aug 2.
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 using in vivo and in vitro methods. 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-based in vitro bioassay, 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.
全氟和多氟烷基物质（PFAS）被发现对人类健康有多种不良影响。最近，流行病学和毒理学研究表明，接触 PFAS 会对胰腺产生不良影响，并与胰岛素异常有关。为了探讨 PFAS 如何导致糖尿病，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细胞活力和胰岛素分泌能力的影响。我们发现，28 天 PFOS（10mg/（kg 体重•天））给药导致雄性小鼠的胰腺重量和胰岛大小减小。PFOS 给药还导致雄性小鼠空腹和葡萄糖输注后血清胰岛素水平降低。在基于细胞的体外生物测定中，我们使用了小鼠β-TC-6 癌细胞，发现 PFOS 暴露 48 小时会降低 50μmol/L 时的细胞活力。通过测量上清液中的胰岛素含量，发现 PFOS（100μmol/L）预处理 48 小时后会降低葡萄糖刺激后β-TC-6 细胞的胰岛素释放能力。尽管这些浓度高于 PFOS 的环境浓度，但考虑到老鼠比人类具有更快的 PFOS 清除效率，老鼠体内 PFOS 浓度较高可能会产生可观察到的毒性作用，这是合理的。PFOS（50μmol/L）暴露于β-TC-6 细胞会导致细胞内活性氧物质（ROS）的积累。过量的 ROS 诱导细胞的反应性毒性，最终引发细胞凋亡和坏死。本研究的结果为接触 PFOS 与糖尿病风险之间可能存在因果关系提供了证据。
