PMID- 31432086 OWN - NLM STAT- MEDLINE DCOM- 20200821 LR - 20200821 IS - 1096-0929 (Electronic) IS - 1096-0929 (Linking) VI - 172 IP - 2 DP - 2019 Dec 1 TI - 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. PG - 359-367 LID - 10.1093/toxsci/kfz192 [doi] AB - Environmental exposure to persistent organic pollutants (POPs) has been suggested as a contributing factor for the increased rate of type 2 diabetes 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 the Total mixture at x500 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 x500. Secretion levels seen for these remained lower than the Total mixture, and the Br mixture had no effect. After 24 h, increased secretion was seen with all mixtures at x1 blood levels. Cytotoxicity was present for x100 and x500 blood levels. When tested in a GLP-1 receptor translocation assay (U2OS-GLP1R-EGFP), neither agonistic nor antagonist effects on receptor internalization were seen for any of the mixtures. We conclude individual classes of POPs, alone or in combination, can affect GLP-1 secretion and may contribute as a molecular mechanism linking environmental toxicants and diabetes. CI - (c) The Author(s) 2019. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Shannon, Maeve AU - Shannon M AD - Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Belfast, BT9 5DL, Northern Ireland, UK. FAU - Xie, Yuling AU - Xie Y AD - Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Belfast, BT9 5DL, Northern Ireland, UK. FAU - Verhaegen, Steven AU - Verhaegen S AD - Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo 0102, Norway. FAU - Wilson, Jodie AU - Wilson J AD - Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Belfast, BT9 5DL, Northern Ireland, UK. FAU - Berntsen, Hanne F AU - Berntsen HF AD - Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo 0102, Norway. AD - Department of Administration, Lab Animal Unit, National Institute of Occupational Health, Oslo 0363, Norway. FAU - Zimmer, Karin E AU - Zimmer KE AD - Department of Basic Sciences and Aquatic Medicine, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo 0102, Norway. FAU - Ropstad, Erik AU - Ropstad E AD - Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo 0102, Norway. FAU - Green, Brian D AU - Green BD AD - Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Belfast, BT9 5DL, Northern Ireland, UK. FAU - Connolly, Lisa AU - Connolly L AD - Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Belfast, BT9 5DL, Northern Ireland, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Toxicol Sci JT - Toxicological sciences : an official journal of the Society of Toxicology JID - 9805461 RN - 0 (Endocrine Disruptors) RN - 0 (Environmental Pollutants) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hydrocarbons, Halogenated) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Cell Culture Techniques MH - Cell Line MH - Cell Survival/drug effects MH - Endocrine Disruptors/chemistry/*toxicity MH - Enteroendocrine Cells/*drug effects/metabolism MH - Environmental Pollutants/chemistry/*toxicity MH - Glucagon-Like Peptide 1/*metabolism MH - Glucagon-Like Peptide-1 Receptor/*metabolism MH - Humans MH - Hydrocarbons, Halogenated/chemistry/*toxicity MH - Protein Transport OTO - NOTNLM OT - ELISA OT - enteroendocrine cell OT - gut hormones OT - high content analysis OT - metabolic disruption OT - mixture EDAT- 2019/08/23 06:00 MHDA- 2020/08/22 06:00 CRDT- 2019/08/22 06:00 PHST- 2019/08/23 06:00 [pubmed] PHST- 2020/08/22 06:00 [medline] PHST- 2019/08/22 06:00 [entrez] AID - 5552164 [pii] AID - 10.1093/toxsci/kfz192 [doi] PST - ppublish SO - Toxicol Sci. 2019 Dec 1;172(2):359-367. doi: 10.1093/toxsci/kfz192.