Importance of Extranuclear Estrogen Receptor- and Membrane G Protein–Coupled Estrogen Receptor in Pancreatic Islet Survival

OBJECTIVE—We showed that 17-estradiol (E2) favors pan-creatic -cell survival via the estrogen receptor- (ER) in mice. E2 activates nuclear estrogen receptors via an estrogen response element (ERE). E2 also activates nongenomic signals via an extranuclear form of ER and the G protein–coupled estrogen receptor (GPER). We studied the contribution of estrogen recep-tors to islet survival. RESEARCH DESIGN AND METHODS—We used mice and islets deficient in estrogen receptor- (ERKO/), estrogen receptor- (ERKO/), estrogen receptor- and estrogen recep-tor- (ERKO/), and GPER (GPERKO/); a mouse lacking ER binding to the ERE; and human islets. These mice and islets were studied in combination with receptor-specific pharmaco-logical probes. RESULTS—We show that ER protection of islet survival i