Objectives: 

Bisphenol-A (BPA) is a widespread endocrine disrupting chemical (EDC) used as the base compound in the manufacture of polycarbonate plastics. In humans, epidemiological evidence associated BPA exposure in adults with higher risk of type-2 diabetes and heart disease. Here we studied the action of environmentally relevant doses of BPA on pancreatic beta cell function and the impact of BPA exposure on glucose homeostasis and insulin sensitivity

Materials: 

Adult mice were treated with either vehicle or BPA (10 or 100 microg/kg/day) during 4 or 8 days. Isolated human and mouse pancreatic islets of Langerhans were exposed to low doses of BPA.

Results: 

Ex vivo experiments show that BPA 1nM blocks ATP-sensitive K+ channels increasing pancreatic insulin secretion in an estrogen receptor beta dependent manner. In vivo experiments indicated that mice exposed to BPA showed a chronic hyperinsulinemia in the fed state and presented altered glucose and insulin sensitivity. Insulin resistance and impaired insulin signaling were manifested in liver and skeletal muscle.

Conclusions: 

Our findings suggest that BPA disrupts pancreatic beta-cell function and peripheral insulin signaling. Therefore, environmental estrogen exposure enhances the risk of developing type 2 diabetes mellitus.