TY - JOUR AU - Shaklai, Sigal AU - Grafi-Cohen, Meital AU - Sharon, Orli AU - Shefer, Gabi AU - Somjen, Dalia AU - Stern, Naftali PY - 2019 DA - 2019/08/27 TI - Estradiol 17-β Induces Pancreatic Beta-Cell Proliferation through Distinct Estrogen Receptors in a Glucose Dependent Manner JO - OBM Transplantation SP - 082 VL - 03 IS - 03 AB - Background: Estradiol 17-beta (E2) enhances the function and survival of pancreatic beta-cells but its clinical use has been questioned due to concerns regarding oncogenic potential and feminizing effects in males. The G-protein coupled estrogen receptor (GPER), expressed in pancreatic islets, exhibits estrogenic beta-cell protective effects, without the feminizing effects of the nuclear ERs. Here, we examine the outcome of selective activation of the three estrogen receptors ERα, ERβ and GPER on replication, in human pancreatic islets and the INS1-E rodent β-cell line, under hyperglycemic conditions such as occur in diabetes mellitus. Methods: Pancreatic islets from nine human donors and INS1-E cells were grown at glucose concentrations of 11mM and 25mM and examined for DNA synthesis using 3[H]-thymidine incorporation, after 24 hour treatment with E2 and specific agonists for ERα, ERβ and GPER (PPT 10nM, DPN 10nM and G1 100nM, respectively). Expression of the three ERs was examined by qRT-PCR. Results: In human islets, under glucose 11mM, agonists to ERα and GPER induced a significant ~2 folds increase in 3[H]-thymidine incorporation (p SN - 2577-5820 UR - https://doi.org/10.21926/obm.transplant.1903082 DO - 10.21926/obm.transplant.1903082 ID - Shaklai2019 ER -