{"doi":"10.2337/db25-0167","title":"The Islet-1 Interaction Partner Rnf20 Regulates Glucose Homeostasis and Pancreatic β-Cell Identity","abstract":"Diabetes is characterized by a loss of functional β-cell mass; therefore, identifying factors involved in establishing and preserving β-cells is critical to combat rising diabetes incidence. While transcription factors are crucial β-cell regulators, knowledge of coregulators facilitating gene expression is limited. Previously, we demonstrated that the islet-1 (Isl1) transcription factor forms complexes with ubiquitin ligases ring finger 20 (Rnf20) and Rnf40 to regulate β-cells in vitro. Here, we investigated whether Rnf20-mediated complexes are required for β-cell function in adult islets by characterizing a novel β-cell-enriched Rnf20 knockout mouse model. Tamoxifen induction of Rnf20 recombination prompted a robust loss of histone 2B monoubiquitination, imparted severe hyperglycemia and glucose intolerance, and elicited an overall reduction in insulin content. Expression of mRNAs and proteins involved in glucose-stimulated insulin secretion and β-cell identity were also dysregulated in Rnf20Δβ-cell mice. Comparative analyses of the loss of either Rnf20 or Isl1 yielded similar changes in the β-cell regulome, supporting that Isl1::Rnf20 complexes are critical regulators of β-cell identity and function. Isl1::Rnf20 complexes are maintained in human tissues wherein they regulate insulin expression, secretion, and content. These findings increase our understanding of key players in β-cell maintenance, which is crucial for the advancement of β-cell derivation diabetes therapeutics. ARTICLE HIGHLIGHTS: Transcription factor Islet-1 (Isl1) and ubiquitin ligase Ring Finger 20 (Rnf20) complexes regulate insulin secretion and β-cell gene expression in vitro. Loss of Rnf20 in adult β-cells disrupts β-cell identity and insulin processing, production, and secretion. In complex with Isl1, Rnf20 influences the β-cell regulome and supports proper glucose homeostasis.","journal":"Diabetes","year":2025,"id":571354,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9535,"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":740817,"name":"Maigen Bethea","orcid":"0000-0001-9847-4885","position":1,"is_corresponding":false},{"id":986086,"name":"Kristen Coutinho","orcid":null,"position":2,"is_corresponding":false},{"id":794109,"name":"Yan-Ping Liu","orcid":"0000-0002-1990-1453","position":3,"is_corresponding":false},{"id":124064,"name":"Jinhua Liu","orcid":"0000-0002-4128-1043","position":4,"is_corresponding":false},{"id":679602,"name":"Min Guo","orcid":"0000-0002-6434-1934","position":5,"is_corresponding":false},{"id":1477501,"name":"Sahil Chada","orcid":null,"position":6,"is_corresponding":false},{"id":288852,"name":"Sylvia Μ. Evans","orcid":"0000-0001-5035-3697","position":7,"is_corresponding":false},{"id":258376,"name":"Wei Li","orcid":"0000-0002-6235-0749","position":8,"is_corresponding":false},{"id":310762,"name":"Sushant Bhatnagar","orcid":"0000-0002-2917-8588","position":9,"is_corresponding":false},{"id":250525,"name":"Roland Stein","orcid":"0000-0001-9192-8661","position":10,"is_corresponding":false},{"id":634761,"name":"Chad S. Hunter","orcid":"0000-0002-1644-447X","position":11,"is_corresponding":false},{"id":566884,"name":"Tanya H. Pierre","orcid":"0000-0001-5177-2463","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T02:57:15.755535Z","pmid":"40743566","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":[]}