US EPA

6315677 

Journal Article 

Perfluoroalkyl Substances Stimulate Insulin Secretion by Islet β Cells via G Protein-Coupled Receptor 40 

Qin, WP; Cao, LY; Li, CH; Guo, LH; Colbourne, J; Ren, XM 

2020 

1 

Environmental Science & Technology
ISSN: 0013-936X
EISSN: 1520-5851 

AMER CHEMICAL SOC 

WASHINGTON 

54 

6 

3428-3436 

English 

32092270 

10.1021/acs.est.9b07295 

WOS:000526416600038 

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 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.