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• W3135428162 endingPage "116840" @default.
• W3135428162 startingPage "116840" @default.
• W3135428162 abstract "Per- and polyfluoroalkyl substances (PFASs) are environmentally and biologically persistent anthropogenic chemicals linked to adverse health outcomes. Epidemiological data have revealed association between exposure to specific PFAS and disruption of insulin level in bodies. However, the effect of PFASs on insulin secretion and the responsible molecular mechanism are poorly understood. In the present study, we used perfluorooctane sulfonate (PFOS) as a representative PFAS family member to investigate its effect on the insulin secretion in mouse pancreatic β cells (β-TC-6). Our results showed that exposure to PFOS inhibited silent information regulator 1 (SIRT1) activity, and molecular simulation showed PFOS could fit into the pocket overlapped with the nicotinamide adenine dinucleotide (NAD+) binding cavity in SIRT1. PFOS exposure upregulated uncoupling protein 2 (UCP2) expression, and this upregulation was blunted in the presence of Ex-527, a SIRT1 specific inhibitor. The mitochondria membrane potential (ΔΨm), as well as the glucose-induced ATP production and Ca2+ influx decreased under PFOS treatment. PFOS continual exposure (48 h) impaired glucose stimulated insulin secretion (GSIS), while the gene expression of insulin was not significantly altered. Importantly, the SIRT1 activator and UCP2 inhibitor could partly reverse the PFOS-induced impairment of GSIS. Taken together, the results suggested that PFOS continual exposure could inhibit SIRT1 activity, and the SIRT1-UCP2 pathway mediated, at least partially, the PFOS induced GSIS impairment." @default.
• W3135428162 created "2021-03-15" @default.
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• W3135428162 date "2021-06-01" @default.
• W3135428162 modified "2023-09-25" @default.
• W3135428162 title "Perfluorooctane sulfonate continual exposure impairs glucose-stimulated insulin secretion via SIRT1-induced upregulation of UCP2 expression" @default.
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• W3135428162 doi "https://doi.org/10.1016/j.envpol.2021.116840" @default.
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