Bisphenol A Is More Potent than Phthalate Metabolites in Reducing Pancreatic β-Cell Function.
Nina Mickelson WeldinghLena Jørgensen-KaurRune BecherJørn A HolmeJohanna Eva BodinUnni Cecilie NygaardAnette Kocbach BøllingPublished in: BioMed research international (2017)
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 pancreatic β-cell line INS-1E, after 2-72 h of exposure to 5-500 μM. Three endpoints relevant to accelerated development of types 1 or 2 diabetes were investigated: β-cell viability, glucose-induced insulin secretion, and β-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 pancreatic β-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.
Keyphrases
- cell death
- high glucose
- diabetic rats
- ms ms
- endothelial cells
- type diabetes
- cardiovascular disease
- drug induced
- blood glucose
- magnetic resonance imaging
- air pollution
- induced apoptosis
- magnetic resonance
- stem cells
- single cell
- anti inflammatory
- mass spectrometry
- metabolic syndrome
- photodynamic therapy
- human health
- cell therapy
- adipose tissue
- endoplasmic reticulum stress
- climate change
- bone marrow