Perfluoroalkyl Substances Stimulate Insulin Secretion by Islet beta Cells via G Protein-Coupled Receptor 40
Perfluoroalkyl Substances Stimulate Insulin Secretion by Islet beta Cells via G Protein-Coupled Receptor 40
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全氟烷基物质通过 G 蛋白偶联受体 40 刺激胰岛 β 细胞分泌胰岛素
DOI：
10.1021/acs.est.9b07295
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发表时间：
2020
影响因子：
11.4
通讯作者：
Ren Xiao-Min
中科院分区：
文献类型：
--
作者：
Qin Wei-Ping;Cao Lin-Ying;Li Chuan-Hai;Guo Liang-Hong;Colbourne John;Ren Xiao-Min
暴露在环境污染物和糖尿病之间的潜在因果关系令人担忧。全氟烷基物质(PFAS)暴露与高胰岛素血症和人类胰岛β细胞胰岛素分泌增加有关，但其潜在机制尚不清楚。通过对野生型和基因敲除小鼠的体内研究和对小鼠胰岛β细胞(β-TC-6)的体外研究，我们清楚地表明，全氟辛烷磺酸(PFOS)暴露1h，通过激活胰岛β细胞上重要的游离脂肪酸调节的膜受体G蛋白偶联受体40(GPR40)，刺激胰岛素分泌和细胞内钙水平。我们通过研究PFASs与人GPR40的分子结合作用，进一步证明了PFASs对小鼠模型的影响也可能在人类中存在。因此，我们为PFASs如何干扰人类胰岛素分泌的新机制提供了证据。
The potential causal relationship between exposure to environmental contaminants and diabetes is troubling. Exposure of perfluoroalkyl substances (PFASs) is found to be associated with hyperinsulinemia and the enhancement of insulin secretion by islet β cells in humans, but the underlying mechanism is still unclear. Here, by combiningin vivostudies with both wild type and gene knockout mice andin vitrostudies with mouse islet β cells (β-TC-6), we demonstrated clearly that 1 h exposure of perfluorooctanesulfonate (PFOS) stimulated insulin secretion and intracellular calcium level by activating G protein-coupled receptor 40 (GPR40), a vital free fatty acid regulated membrane receptor on islet β cells. We further showed that the observed effects of PFASs on the mouse model may also exist in humans by investigating the molecular binding interaction of PFASs with human GPR40. We thus provided evidence for a novel mechanism for how insulin-secretion is disrupted by PFASs in humans.