title: Bisphenol A Is More Potent than Phthalate Metabolites in Reducing Pancreaticβ-Cell Function.
abstract: Bisphenol A (BPA) and phthalates are common environmental contaminants that have been proposed to influence incidence and development of types 1 and 2 diabetes. Thus, effects of BPA and three phthalate metabolites (monoisobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), and mono-(2-ethylhexyl) phthalate (MEHP)) were studied in the pancreaticβ-cell line INS-1E, after 2-72 h of exposure to 5-500μM. Three endpoints relevant to accelerated development of types 1 or 2 diabetes were investigated:β-cell viability, glucose-induced insulin secretion, andβ-cell susceptibility to cytokine-induced cell death. BPA and the phthalate metabolites reduced cellular viability after 72 h of exposure, with BPA as the most potent chemical. Moreover, BPA, MEHP, and MnBP increased insulin secretion after 2 h of simultaneous exposure to chemicals and glucose, with potency BPA > MEHP > MnBP. Longer chemical exposures (24-72 h) showed no consistent effects on glucose-induced insulin secretion, and none of the environmental chemicals affected susceptibility to cytokine-induced cell death. Overall, BPA was more potent than the investigated phthalate metabolites in affecting insulin secretion and viability in the INS-1E pancreaticβ-cells. In contrast to recent literature, concentrations with relevance to human exposures (1-500 nM) did not affect the investigated endpoints, suggesting that this experimental model displayed relatively low sensitivity to environmental chemical exposure.
authors.affiliation: Domain of Infection Control and Environmental Health, Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, 0403 Oslo, Norway.
authors.forename: Nina Mickelson
authors.initials: NM
authors.lastname: Weldingh
authors.affiliation: Domain of Infection Control and Environmental Health, Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, 0403 Oslo, Norway.
authors.forename: Lena
authors.initials: L
authors.lastname: Jørgensen-Kaur
authors.affiliation: Domain of Infection Control and Environmental Health, Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, 0403 Oslo, Norway.
authors.forename: Rune
authors.identifier: 0000-0002-2962-7187
authors.initials: R
authors.lastname: Becher
authors.affiliation: Domain of Infection Control and Environmental Health, Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, 0403 Oslo, Norway.
authors.forename: Jørn A
authors.initials: JA
authors.lastname: Holme
authors.affiliation: Domain of Infection Control and Environmental Health, Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, 0403 Oslo, Norway.
authors.forename: Johanna
authors.identifier: 0000-0001-6556-3486
authors.initials: J
authors.lastname: Bodin
authors.affiliation: Domain of Infection Control and Environmental Health, Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, 0403 Oslo, Norway.
authors.forename: Unni C
authors.identifier: 0000-0002-2955-9970
authors.initials: UC
authors.lastname: Nygaard
authors.affiliation: Domain of Infection Control and Environmental Health, Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, 0403 Oslo, Norway.
authors.forename: Anette Kocbach
authors.identifier: 0000-0003-4209-7448
authors.initials: AK
authors.lastname: Bølling
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004781:Environmental Exposure / Q000009:adverse effects; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D010636:Phenols / Q000493:pharmacokinetics / Q000633:toxicity*; D010795:Phthalic Acids / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D007328:Insulin; D010636:Phenols; D010795:Phthalic Acids; C032279:phthalic acid; C006780:bisphenol A; D000098826:Bisphenol A Compounds