TY - JOUR
T1 - A Human Relevant Defined Mixture of Persistent Organic Pollutants (POPs) Affects In Vitro Secretion of Glucagon-Like Peptide 1 (GLP-1), but Does not Affect Translocation of its Receptor
AU - Shannon, Maeve
AU - Xie, Yuling
AU - Verhaegen, Steven
AU - Wilson, Jodie
AU - Berntsen, Hanne Friis
AU - Zimmer, Karin Elisabeth
AU - Ropstad, Erik
AU - Green, Brian
AU - Connolly, Lisa
N1 - © The Author(s) 2019. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
PY - 2019/12
Y1 - 2019/12
N2 - Environmental exposure to persistent organic pollutants (POPs) has been suggested as a contributing factor for the increased rate of T2D and obesity. A complex mixture of 29 POPs (Total mixture), based on human blood concentrations was used to expose a glucagon-like peptide 1 (GLP-1) secreting enteroendocrine cell line (pGIP/neo: STC-1) in vitro, for 3 and 24 h. Significant increases of GLP-1 occurred when cells were exposed to Total Mixture at x 500 blood levels. Six sub-mixtures representing chlorinated (Cl), brominated (Br), and perfluorinated chemicals (PFAA), and their combinations (Cl + Br, Cl + PFAA, Br + PFAA) were also tested at x 500. Secretion levels seen for these, remained lower than for the Total mixture, and the Br mixture had no effect. After 24 h, increased secretion was seen with all mixtures at x 1 blood levels. Cytotoxicity was present for x 100 and x 500 blood levels. When tested in a GLP-1 receptor translocation assay (U2OS-GLP1R-EGFP), neither agonistic, nor antagonist effects on receptor internalisation were seen for any of the mixtures. We conclude individual classes of POP, alone or in combination, can affect GLP-1 secretion and might contribute as a molecular mechanism, linking environmental toxicants and diabetes.
AB - Environmental exposure to persistent organic pollutants (POPs) has been suggested as a contributing factor for the increased rate of T2D and obesity. A complex mixture of 29 POPs (Total mixture), based on human blood concentrations was used to expose a glucagon-like peptide 1 (GLP-1) secreting enteroendocrine cell line (pGIP/neo: STC-1) in vitro, for 3 and 24 h. Significant increases of GLP-1 occurred when cells were exposed to Total Mixture at x 500 blood levels. Six sub-mixtures representing chlorinated (Cl), brominated (Br), and perfluorinated chemicals (PFAA), and their combinations (Cl + Br, Cl + PFAA, Br + PFAA) were also tested at x 500. Secretion levels seen for these, remained lower than for the Total mixture, and the Br mixture had no effect. After 24 h, increased secretion was seen with all mixtures at x 1 blood levels. Cytotoxicity was present for x 100 and x 500 blood levels. When tested in a GLP-1 receptor translocation assay (U2OS-GLP1R-EGFP), neither agonistic, nor antagonist effects on receptor internalisation were seen for any of the mixtures. We conclude individual classes of POP, alone or in combination, can affect GLP-1 secretion and might contribute as a molecular mechanism, linking environmental toxicants and diabetes.
U2 - 10.1093/toxsci/kfz192
DO - 10.1093/toxsci/kfz192
M3 - Article
C2 - 31432086
VL - 172
SP - 359
EP - 367
JO - Toxicological Sciences
JF - Toxicological Sciences
SN - 1096-6080
IS - 2
ER -