Exposure to bisphenol A induces dysfunction of insulin secretion and apoptosis through the damage of mitochondria in rat insulinoma (INS-1) cells

Cell Death Dis. 2013 Jan 17;4(1):e460. doi: 10.1038/cddis.2012.206.


Bisphenol A (BPA) is widely used in plastic products, through which humans are exposed to it. Accumulating evidence suggests that BPA exposure is associated with β-cell dysfunction. Mitochondrial defects can cause impairment and failure of β cells, but there is little information about the effects of BPA on the mitochondrial function of β cells. In this study, we assessed the role of mitochondria-mediated mechanisms underlying BPA-induced β-cell dysfunction and resulting β-cell apoptosis. INS-1 cells were cultured with 0, 0.0020, 0.020, 0.20, or 2.0 μM BPA. Cell viability, glucose-stimulated insulin secretion (GSIS), and mitochondrial function were examined. The mitochondrial apoptotic pathway was also analyzed at molecular level. We found that BPA suppressed cell viability and disturbed GSIS in a dose-dependent manner. Positive Annexin- propidium iodide (PI) staining and altered expression of Bcl-2 family members and caspases in INS-1 cells indicated that the cells progressively became apoptotic after BPA exposure. Additionally, BPA-induced apoptosis was associated with mitochondrial defects in β cells, as evidenced by depletion of ATP, release of cytochrome c, loss of mitochondrial mass and membrane potential, and alterations in expression of genes involved in mitochondrial function and metabolism. Taken together, these findings provide strong evidence that BPA triggers INS-1 cells dysfunction and apoptosis may be meditated via the mitochondrial pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Apoptosis / drug effects*
  • Benzhydryl Compounds / toxicity*
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cytochromes c / metabolism
  • Glucose / pharmacology
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulinoma / metabolism
  • Insulinoma / pathology
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Phenols / toxicity*
  • Rats


  • Benzhydryl Compounds
  • Insulin
  • Phenols
  • Adenosine Triphosphate
  • Cytochromes c
  • Caspases
  • Glucose
  • bisphenol A