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

Toxicol Sci. 2019 Dec 1;172(2):359-367. doi: 10.1093/toxsci/kfz192.


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 ×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 ×500. 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 ×1 blood levels. Cytotoxicity was present for ×100 and ×500 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.

Keywords: ELISA; enteroendocrine cell; gut hormones; high content analysis; metabolic disruption; mixture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques
  • Cell Line
  • Cell Survival / drug effects
  • Endocrine Disruptors / chemistry
  • Endocrine Disruptors / toxicity*
  • Enteroendocrine Cells / drug effects*
  • Enteroendocrine Cells / metabolism
  • Environmental Pollutants / chemistry
  • Environmental Pollutants / toxicity*
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucagon-Like Peptide-1 Receptor / metabolism*
  • Humans
  • Hydrocarbons, Halogenated / chemistry
  • Hydrocarbons, Halogenated / toxicity*
  • Protein Transport


  • Endocrine Disruptors
  • Environmental Pollutants
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Hydrocarbons, Halogenated
  • Glucagon-Like Peptide 1