Croucher Institute for Environmental Sciences, Department of Biology, Hong Kong Baptist University, Hong Kong SAR, China.
School of Life Sciences, Hong Kong Bioinformatics Centre, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
Environ Pollut. 2021 Nov 15;289:117857. doi: 10.1016/j.envpol.2021.117857. Epub 2021 Jul 26.
Considerable human data have shown that the exposure to perfluorooctane sulfonate (PFOS) correlates to the risk of metabolic diseases, however the underlying effects are not clearly elucidated. In this study, we investigated the impacts of PFOS treatment, using in-vivo, ex-vivo and in-vitro approaches, on pancreatic β-cell functions. Mice were oral-gavage with 1 and 5 μg PFOS/g body weight/day for 21 days. The animals showed a significant increase in liver triglycerides, accompanied by a reduction of triglycerides in blood sera and glycogen in livers and muscles. Histological examination of pancreases showed no noticeable changes in the size and number of islets from the control and treatment groups. Immunohistochemistry showed a reduction of staining intensities of insulin and the transcriptional factors (Pdx-1, islet-1) in islets of pancreatic sections from PFOS-treated groups, but no changes in the intensity of Glut2 and glucagon were noted. Transcriptomic study of isolated pancreatic islets treated ex vivo with 1 μM and 10 μM PFOS for 24 h, underlined perturbations of the insulin signaling pathways. Western blot analysis of ex-vivo PFOS-treated islets revealed a significant reduction in the expression levels of the insulin receptor, the IGF1 receptor-β, Pdk1-Akt-mTOR pathways, and Pdx-1. Using the mouse β-cells (Min-6) treated with 1 μM and 10 μM PFOS for 24 h, Western blot analysis consistently showed the PFOS-treatment inhibited Akt-pathway and reduced cellular insulin contents. Moreover, functional studies revealed the inhibitory effects of PFOS on glucose-stimulated insulin-secretion (GSIS) and the rate of ATP production. Our data support the perturbing effects of PFOS on animal metabolism and demonstrate the underlying molecular targets to impair β-cell functions.
大量的人类数据表明，全氟辛烷磺酸（PFOS）的暴露与代谢疾病的风险相关，但潜在的影响尚不清楚。在这项研究中，我们通过体内、体外和离体方法研究了 PFOS 处理对胰腺β细胞功能的影响。将 1 和 5μg PFOS/g 体重/天的剂量通过口服灌胃的方式给予小鼠，持续 21 天。结果显示，实验组动物的肝脏甘油三酯明显增加，同时血清中的甘油三酯和肝脏及肌肉中的糖原减少。对胰腺的组织学检查显示，对照组和处理组的胰岛大小和数量没有明显变化。免疫组化显示，PFOS 处理组胰腺切片中胰岛的胰岛素和转录因子（Pdx-1、胰岛-1）染色强度降低，但 Glut2 和胰高血糖素的强度没有变化。离体研究显示，1μM 和 10μM PFOS 处理离体胰岛 24 小时后，胰岛素信号通路受到干扰。离体 PFOS 处理的胰岛 Western blot 分析显示，胰岛素受体、IGF1 受体-β、Pdk1-Akt-mTOR 通路和 Pdx-1 的表达水平显著降低。用 1μM 和 10μM PFOS 处理 24 小时的小鼠β细胞（Min-6）的 Western blot 分析结果一致表明，PFOS 处理抑制了 Akt 通路并减少了细胞内胰岛素含量。此外，功能研究显示 PFOS 对葡萄糖刺激的胰岛素分泌（GSIS）和 ATP 产生速率具有抑制作用。我们的数据支持 PFOS 对动物代谢的干扰作用，并证明了损害β细胞功能的潜在分子靶点。
