Bisphenol A (BPA) can disrupt glucose homeostasis and impair pancreatic islet 
function; however, the mechanisms behind these effects are poorly understood. 
Male mice (4 wk old) were treated with BPA (50 or 500 μg/kg/d) for 8 wk. 
Whole-body glucose homeostasis, pancreatic islet morphology and function, and 
miR-338-mediated molecular signal transduction analyses were examined. We showed 
that BPA treatment led to a disruption of glucose tolerance and a compensatory 
increase of pancreatic islets insulin secretion and pancreatic and duodenal 
homeobox 1 (Pdx1) expression in mice. Inhibition of Pdx1 reduced 
glucose-stimulated insulin secretion and ATP production in the islets of 
BPA-exposed mice. Based on primary pancreatic islets, we also confirmed that 
miR-338 regulated Pdx1 and thus contributed to BPA-induced insulin secretory 
dysfunction from compensation to decompensation. Short-term BPA exposure 
downregulated miR-338 through activation of G-protein-coupled estrogen receptor 
1 (Gpr30), whereas long-term BPA exposure upregulated miR-338 through 
suppression of glucagon-like peptide 1 receptor (Glp1r). Taken together, our 
results reveal a molecular mechanism, whereby BPA regulates Gpr30/Glp1r to 
mediate the expression of miR-338, which acts to control Pdx1-dependent insulin 
secretion. The Gpr30/Glp1r-miR-338-Pdx1 axis should be represented as a novel 
mechanism by which BPA induces insulin secretory dysfunction in pancreatic 
islets.-Wei, J., Ding, D., Wang, T., Liu, Q., Lin, Y. MiR-338 controls 
BPA-triggered pancreatic islet insulin secretory dysfunction from compensation 
to decompensation by targeting Pdx-1.