Cargando…
In Vitro Assays to Identify Metabolism-Disrupting Chemicals with Diabetogenic Activity in a Human Pancreatic β-Cell Model
There is a need to develop identification tests for Metabolism Disrupting Chemicals (MDCs) with diabetogenic activity. Here we used the human EndoC-βH1 β-cell line, the rat β-cell line INS-1E and dispersed mouse islet cells to assess the effects of endocrine disruptors on cell viability and glucose-...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9102687/ https://www.ncbi.nlm.nih.gov/pubmed/35563431 http://dx.doi.org/10.3390/ijms23095040 |
_version_ | 1784707387420049408 |
---|---|
author | Dos Santos, Reinaldo Sousa Medina-Gali, Regla María Babiloni-Chust, Ignacio Marroqui, Laura Nadal, Angel |
author_facet | Dos Santos, Reinaldo Sousa Medina-Gali, Regla María Babiloni-Chust, Ignacio Marroqui, Laura Nadal, Angel |
author_sort | Dos Santos, Reinaldo Sousa |
collection | PubMed |
description | There is a need to develop identification tests for Metabolism Disrupting Chemicals (MDCs) with diabetogenic activity. Here we used the human EndoC-βH1 β-cell line, the rat β-cell line INS-1E and dispersed mouse islet cells to assess the effects of endocrine disruptors on cell viability and glucose-stimulated insulin secretion (GSIS). We tested six chemicals at concentrations within human exposure (from 0.1 pM to 1 µM). Bisphenol-A (BPA) and tributyltin (TBT) were used as controls while four other chemicals, namely perfluorooctanoic acid (PFOA), triphenylphosphate (TPP), triclosan (TCS) and dichlorodiphenyldichloroethylene (DDE), were used as “unknowns”. Regarding cell viability, BPA and TBT increased cell death as previously observed. Their mode of action involved the activation of estrogen receptors and PPARγ, respectively. ROS production was a consistent key event in BPA-and TBT-treated cells. None of the other MDCs tested modified viability or ROS production. Concerning GSIS, TBT increased insulin secretion while BPA produced no effects. PFOA decreased GSIS, suggesting that this chemical could be a “new” diabetogenic agent. Our results indicate that the EndoC-βH1 cell line is a suitable human β-cell model for testing diabetogenic MDCs. Optimization of the test methods proposed here could be incorporated into a set of protocols for the identification of MDCs. |
format | Online Article Text |
id | pubmed-9102687 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91026872022-05-14 In Vitro Assays to Identify Metabolism-Disrupting Chemicals with Diabetogenic Activity in a Human Pancreatic β-Cell Model Dos Santos, Reinaldo Sousa Medina-Gali, Regla María Babiloni-Chust, Ignacio Marroqui, Laura Nadal, Angel Int J Mol Sci Article There is a need to develop identification tests for Metabolism Disrupting Chemicals (MDCs) with diabetogenic activity. Here we used the human EndoC-βH1 β-cell line, the rat β-cell line INS-1E and dispersed mouse islet cells to assess the effects of endocrine disruptors on cell viability and glucose-stimulated insulin secretion (GSIS). We tested six chemicals at concentrations within human exposure (from 0.1 pM to 1 µM). Bisphenol-A (BPA) and tributyltin (TBT) were used as controls while four other chemicals, namely perfluorooctanoic acid (PFOA), triphenylphosphate (TPP), triclosan (TCS) and dichlorodiphenyldichloroethylene (DDE), were used as “unknowns”. Regarding cell viability, BPA and TBT increased cell death as previously observed. Their mode of action involved the activation of estrogen receptors and PPARγ, respectively. ROS production was a consistent key event in BPA-and TBT-treated cells. None of the other MDCs tested modified viability or ROS production. Concerning GSIS, TBT increased insulin secretion while BPA produced no effects. PFOA decreased GSIS, suggesting that this chemical could be a “new” diabetogenic agent. Our results indicate that the EndoC-βH1 cell line is a suitable human β-cell model for testing diabetogenic MDCs. Optimization of the test methods proposed here could be incorporated into a set of protocols for the identification of MDCs. MDPI 2022-05-01 /pmc/articles/PMC9102687/ /pubmed/35563431 http://dx.doi.org/10.3390/ijms23095040 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Dos Santos, Reinaldo Sousa Medina-Gali, Regla María Babiloni-Chust, Ignacio Marroqui, Laura Nadal, Angel In Vitro Assays to Identify Metabolism-Disrupting Chemicals with Diabetogenic Activity in a Human Pancreatic β-Cell Model |
title | In Vitro Assays to Identify Metabolism-Disrupting Chemicals with Diabetogenic Activity in a Human Pancreatic β-Cell Model |
title_full | In Vitro Assays to Identify Metabolism-Disrupting Chemicals with Diabetogenic Activity in a Human Pancreatic β-Cell Model |
title_fullStr | In Vitro Assays to Identify Metabolism-Disrupting Chemicals with Diabetogenic Activity in a Human Pancreatic β-Cell Model |
title_full_unstemmed | In Vitro Assays to Identify Metabolism-Disrupting Chemicals with Diabetogenic Activity in a Human Pancreatic β-Cell Model |
title_short | In Vitro Assays to Identify Metabolism-Disrupting Chemicals with Diabetogenic Activity in a Human Pancreatic β-Cell Model |
title_sort | in vitro assays to identify metabolism-disrupting chemicals with diabetogenic activity in a human pancreatic β-cell model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9102687/ https://www.ncbi.nlm.nih.gov/pubmed/35563431 http://dx.doi.org/10.3390/ijms23095040 |
work_keys_str_mv | AT dossantosreinaldosousa invitroassaystoidentifymetabolismdisruptingchemicalswithdiabetogenicactivityinahumanpancreaticbcellmodel AT medinagalireglamaria invitroassaystoidentifymetabolismdisruptingchemicalswithdiabetogenicactivityinahumanpancreaticbcellmodel AT babilonichustignacio invitroassaystoidentifymetabolismdisruptingchemicalswithdiabetogenicactivityinahumanpancreaticbcellmodel AT marroquilaura invitroassaystoidentifymetabolismdisruptingchemicalswithdiabetogenicactivityinahumanpancreaticbcellmodel AT nadalangel invitroassaystoidentifymetabolismdisruptingchemicalswithdiabetogenicactivityinahumanpancreaticbcellmodel |