{"doi":"10.1101/2025.05.12.652914","title":"G Protein Coupled Estrogen Receptor Signaling Maintains β Cell Identity in Female Mice","abstract":"ABSTRACT Type 2 diabetes (T2D) arises in the context of obesity and overnutrition; however, additional demographic features including age and biological sex contribute to T2D risk. Estradiol (E2) is thought to play a protective metabolic role that may govern sex differences in the development of T2D. The mechanisms by which E2 exerts these effects and the impact of reduced E2 signaling in β cells during menopause remain incompletely understood. We analyzed publicly available whole islet transcriptome datasets from female and male cadaveric donors and showed significant age-related modulation of gene expression, including changes in pathways related to β cell function, in islets from female donors. Importantly, these patterns were not observed in islets from male donors. To test the in vivo relationship between E2 signaling and β cell function, 10-week- old female C57BL6/J mice underwent an ovariectomy (OVX) or sham (CTR) surgery, followed by 4 weeks of high-fat diet (HFD) treatment. HFD-OVX mice exhibited obesity-induced glucose intolerance, increased α cell mass, and reduced expression of β cell identity markers. Furthermore, ex vivo treatment of islets with the G protein coupled estrogen receptor (GPER)- specific agonist G-1 restored β cell identity gene expression. Together, these data identify a novel connection between GPER signaling and β cell identity and suggest that menopausal loss of E2 signaling through GPER may be linked with loss of β cell identity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":557907,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":332525,"name":"Preethi Krishnan","orcid":"0000-0001-6957-385X","position":1,"is_corresponding":false},{"id":57841,"name":"Wenting Wu","orcid":"0000-0003-0982-771X","position":2,"is_corresponding":false},{"id":718138,"name":"Cameron R. Rostron","orcid":"0000-0003-4727-3420","position":3,"is_corresponding":false},{"id":382490,"name":"Kara S. Orr","orcid":"0000-0002-1321-8581","position":4,"is_corresponding":false},{"id":410635,"name":"Lata Udari","orcid":null,"position":5,"is_corresponding":false},{"id":1311626,"name":"Jacqueline Del Carmen Aquino","orcid":null,"position":6,"is_corresponding":false},{"id":436673,"name":"Amanda Fisher","orcid":null,"position":7,"is_corresponding":false},{"id":461853,"name":"Tatsuyoshi Kono","orcid":"0000-0002-7524-6836","position":8,"is_corresponding":false},{"id":515010,"name":"Kok Lim Kua","orcid":"0000-0002-6351-4506","position":9,"is_corresponding":false},{"id":7388,"name":"Carmella Evans‐Molina","orcid":"0000-0001-7764-8663","position":10,"is_corresponding":false},{"id":1457954,"name":"Madeline R. McLaughlin","orcid":"0000-0001-8878-9648","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:55:21.727661Z","pmid":"40463047","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}