Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin 300350, China; School of Environmental Science and Safety Engineering, Tianjin University of Technology, Tianjin 300384, China.
Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin 300350, China.
Sci Total Environ. 2020 Jul 15;726:138498. doi: 10.1016/j.scitotenv.2020.138498. Epub 2020 Apr 7.
Perfluoroalkyl substances (PFASs) are widely used synthetic chemicals, showing environmental/biological persistence and adverse effects on ecosystem and human health. Several epidemiological and animal studies have revealed that PFASs levels are associated with elevated serum insulin level; however, the effect of PFASs on insulin secretion and the underlying mechanism are not clear. In this study, the effect of a most concerned PFAS, perfluorooctane sulfonate (PFOS) on insulin secretion in Beta-TC-6 pancreatic cells was studied. The results showed that PFOS acute exposure stimulated insulin secretion and elevated intracellular calcium concentration ([Ca]). The PFOS-stimulated [Ca] elevation was resulted from both extra- and intra-cellular sources. PFOS acute exposure decreased ATP content and ATP/ADP ratio, indicating the mitochondrial function was damaged under PFOS acute exposure. The PFOS-stimulated insulin secretion was inhibited by GW1100, a G Protein-coupled Receptor 40 (GPR40) specific inhibitor, but not affected by GW9662, a specific antagonist to the peroxisome proliferator-activated receptor gamma (PPARγ). The observation of RNA silencing further demonstrated that the PFOS-stimulated insulin secretion is, at least partially, via GPR40. By using specific inhibitors, we found that the GPR40 downstream pathways, phospholipase C (PLC) and L-type Ca channels (LTCC) were involved in PFOS-stimulated [Ca] elevation and insulin secretion.
全氟烷基物质 (PFASs) 是广泛使用的合成化学品，具有环境/生物持久性，并对生态系统和人类健康产生不良影响。几项流行病学和动物研究表明，PFASs 水平与血清胰岛素水平升高有关；然而，PFASs 对胰岛素分泌的影响及其潜在机制尚不清楚。在这项研究中，研究了最受关注的 PFAS 之一——全氟辛烷磺酸 (PFOS) 对 Beta-TC-6 胰腺细胞胰岛素分泌的影响。结果表明，PFOS 急性暴露刺激胰岛素分泌并升高细胞内钙离子浓度 ([Ca])。PFOS 刺激的 [Ca] 升高来自细胞外和细胞内来源。PFOS 急性暴露降低了 ATP 含量和 ATP/ADP 比值，表明线粒体功能在 PFOS 急性暴露下受损。G 蛋白偶联受体 40 (GPR40) 特异性抑制剂 GW1100 抑制了 PFOS 刺激的胰岛素分泌，但对过氧化物酶体增殖物激活受体 γ (PPARγ) 的特异性拮抗剂 GW9662 没有影响。RNA 沉默的观察进一步表明，PFOS 刺激的胰岛素分泌至少部分是通过 GPR40 介导的。通过使用特异性抑制剂，我们发现 GPR40 下游途径，即磷脂酶 C (PLC) 和 L 型钙通道 (LTCC)，参与了 PFOS 刺激的 [Ca] 升高和胰岛素分泌。
