Bisphenol A Is More Potent than Phthalate Metabolites in Reducing Pancreatic [beta]-Cell Function

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.