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Toxicol Sci. 2019 Aug 20. pii: kfz192. doi: 10.1093/toxsci/kfz192. [Epub ahead of print]

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.

Author information

1
Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Northern Ireland, United Kingdom.
2
Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Postboks 369 sentrum, Oslo, Norway.
3
Department of Administration, Lab Animal Unit, National Institute of Occupational Health, P.O. Box 5330, Oslo, Norway.
4
Department of Basic Sciences and Aquatic Medicine, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Postboks 369 sentrum, Oslo, Norway.

Abstract

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.

KEYWORDS:

ELISA; Enteroendocrine cell; Gut hormones; High Content Analysis; Metabolic disruption; Mixture

PMID:
31432086
DOI:
10.1093/toxsci/kfz192

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