Characterization of PFOS toxicity on in-vivo and ex-vivo mouse pancreatic islets

Considerable human data have shown that the exposure to perfluorooctane sulfonate (PFOS) correlates to the risk of metabolic diseases, however the underlying effects are not clearly elucidated. In this study, we investigated the impacts of PFOS treatment, using in-vivo, ex-vivo and in-vitro approaches, on pancreatic β-cell functions. Mice were oral-gavage with 1 and 5 μg PFOS/g body weight/day for 21 days. The animals showed a significant increase in liver triglycerides, accompanied by a reduction of triglycerides in blood sera and glycogen in livers and muscles. Histological examination of pancreases showed no noticeable changes in the size and number of islets from the control and treatment groups. Immunohistochemistry showed a reduction of staining intensities of insulin and the transcriptional factors (Pdx-1, islet-1) in islets of pancreatic sections from PFOS-treated groups, but no changes in the intensity of Glut2 and glucagon were noted. Transcriptomic study of isolated pancreatic islets treated ex vivo with 1 μM and 10 μM PFOS for 24 h, underlined perturbations of the insulin signaling pathways. Western blot analysis of ex-vivo PFOS-treated islets revealed a significant reduction in the expression levels of the insulin receptor, the IGF1 receptor-β, Pdk1-Akt-mTOR pathways, and Pdx-1. Using the mouse β-cells (Min-6) treated with 1 μM and 10 μM PFOS for 24 h, Western blot analysis consistently showed the PFOS-treatment inhibited Akt-pathway and reduced cellular insulin contents. Moreover, functional studies revealed the inhibitory effects of PFOS on glucose-stimulated insulin-secretion (GSIS) and the rate of ATP production. Our data support the perturbing effects of PFOS on animal metabolism and demonstrate the underlying molecular targets to impair β-cell functions.