摘要
Per-and polyfluoroalkyl substances(PFAS)are found to have multiple adverse outcomes on human health.Recently,epidemiological and toxicological studies showed that exposure to PFAS had adverse impacts on pancreas and showed association with insulin abnormalities.To explore how PFAS may contribute to diabetes,we studied impacts of perfluorooctane sul-fonate(PFOS)on cell viability and insulin release capacity of pancreatic β cells by using in vivo and in vitro methods.We found that 28-day administration with PFOS(10 mg/(kg body weight·day))caused reductions of pancreas weight and islet size in male mice.PFOS admin-istration also led to lower serum insulin level both in fasting state and after glucose infusion among male mice.For cell-based in vitro bioassay,we used mouse β-TC-6 cancer cells and found 48-hr exposure to PFOS decreased the cell viability at 50 μmol/L.By measuring insulin content in supernatant,48-hr pretreatment of PFOS(100 μmol/L)decreased the insulin re-lease capacity of β-TC-6 cells after glucose stimulation.Although these concentrations were higher than the environmental concentration of PFOS,it might be reasonable for high con-centration of PFOS to exert observable toxic effects in mice considering mice had a faster removal efficiency of PFOS than human.PFOS exposure(50 μmol/L)to β-TC-6 cells induced intracellular accumulation of reactive oxidative specie(ROS).Excessive ROS induced the re-active toxicity of cells,which eventually invoke apoptosis and necrosis.Results in this study provide evidence for the possible causal link of exposure to PFOS and diabetes risk.
基金
This work was supported by the National Natural Science Foundation of China(Nos.U20A20133,21777187)
the Royal Society International Collaboration Award for Research Professors(No.IC160121).
