Estradiol Prevents High Glucose-Induced β-cell Apoptosis by Decreased BTG2 Expression

Hyperglycemia stimulates several pathways to induce pancreatic β-cell apoptosis. In our previous study by mRNA analysis, we demonstrated that B-cell translocation gene 2 (BTG(2)) expression was up-regulated in INS-1 cells cultured under high glucose conditions, but this effect was reversed by estrogen. In the present study, we demonstrated that BTG(2) mRNA and protein expressions in both INS-1 cells and mouse pancreatic islets increased under high glucose conditions compared to those cultured under basal glucose conditions, while in the presence of estrogen, the BTG(2) mRNA and protein expressions decreased. SiRNA-BTG(2) significantly reduced cell apoptosis, cleaved-caspase 3, and Bax, compared to the siRNA-control in INS-1 cultured under high glucose conditions. We further demonstrated that BTG(2) promoter activity was activated under high glucose conditions whereas estrogen significantly reduced it. The effects of estrogen on BTG(2) expression were inhibited by estrogen receptor inhibitors. Also, under high glucose conditions, p53 and Bax mRNA and protein expressions increased, but they decreased in the presence of estrogen. Again, the effect of estrogen on p53 and Bax expression was inhibited by estrogen receptor inhibitors. Taken together, this study demonstrates that estrogen reduces pancreatic β-cell apoptosis under high glucose conditions via suppression of BTG2, p53, and Bax expressions.