es9b07295_si_001.pdf (1.19 MB)
Perfluoroalkyl Substances Stimulate Insulin Secretion by Islet β Cells via G Protein-Coupled Receptor 40
journal contribution
posted on 2020-03-05, 18:20 authored by Wei-Ping Qin, Lin-Ying Cao, Chuan-Hai Li, Liang-Hong Guo, John Colbourne, Xiao-Min RenThe
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.