Perfluorooctane sulfonate acute exposure stimulates insulin secretion via GPR40 pathway.

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 ([Ca2+]i). The PFOS-stimulated [Ca2+]i 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 Ca2+ channels (LTCC) were involved in PFOS-stimulated [Ca2+]i elevation and insulin secretion.