Perfluoroalkyl Substances Stimulate Insulin Secretion by Islet β Cells via G Protein-Coupled Receptor 40
By Wei-Ping Qin, Lin-Ying Cao, Chuan-Hai Li, Liang-Hong Guo, John K Colbourne, and Xiao-Min Ren
Environ. Sci. Technol.
March 3, 2020
DOI: 10.1021/acs.est.9b07295
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 combining in vivo studies with both wild type and gene knockout mice and in vitro studies with mouse islet β cells (β-TC-6), we demonstrated clearly that one-hour exposure of perfluorooctane sulfonate (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 mouse model may also exist on human 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 human.
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