{"doi":"10.1172/jci.insight.166386","title":"Species-specific roles for the MAFA and MAFB transcription factors in regulating islet β cell identity","abstract":"Type 2 diabetes (T2D) is associated with compromised identity of insulin-producing pancreatic islet β cells, characterized by inappropriate production of other islet cell-enriched hormones. Here, we examined how hormone misexpression was influenced by the MAFA and MAFB transcription factors, closely related proteins that maintain islet cell function. Mice specifically lacking MafA in β cells demonstrated broad, population-wide changes in hormone gene expression with an overall gene signature closely resembling islet gastrin+ (Gast+) cells generated under conditions of chronic hyperglycemia and obesity. A human β cell line deficient in MAFB, but not one lacking MAFA, also produced a GAST+ gene expression pattern. In addition, GAST was detected in human T2D β cells with low levels of MAFB. Moreover, evidence is provided that human MAFB can directly repress GAST gene transcription. These results support a potentially novel, species-specific role for MafA and MAFB in maintaining adult mouse and human β cell identity, respectively. Here, we discuss the possibility that induction of Gast/GAST and other non-β cell hormones, by reduction in the levels of these transcription factors, represents a dysfunctional β cell signature.","journal":"JCI Insight","year":2023,"id":361090,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9582,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":461847,"name":"Xin Tong","orcid":"0000-0003-4408-3832","position":1,"is_corresponding":false},{"id":320873,"name":"Emily M. Walker","orcid":"0000-0001-8394-1567","position":2,"is_corresponding":false},{"id":1010483,"name":"Tehila Dahan","orcid":null,"position":3,"is_corresponding":false},{"id":398588,"name":"Veronica A. Cochrane","orcid":null,"position":4,"is_corresponding":false},{"id":1010049,"name":"Sudipta Ashe","orcid":"0000-0002-7011-1078","position":5,"is_corresponding":false},{"id":322075,"name":"Ronan Russell","orcid":null,"position":6,"is_corresponding":false},{"id":289721,"name":"Anna B. Osipovich","orcid":"0000-0002-9513-2262","position":7,"is_corresponding":false},{"id":817751,"name":"Alex M. Mawla","orcid":"0000-0003-0907-464X","position":8,"is_corresponding":false},{"id":679602,"name":"Min Guo","orcid":"0000-0002-6434-1934","position":9,"is_corresponding":false},{"id":679603,"name":"Jinhua Liu","orcid":"0000-0002-5592-5954","position":10,"is_corresponding":false},{"id":1113280,"name":"Zachary A. Loyd","orcid":"0009-0000-7549-5253","position":11,"is_corresponding":false},{"id":7355,"name":"Mark O. Huising","orcid":"0000-0002-6594-2205","position":12,"is_corresponding":false},{"id":289722,"name":"Mark A. Magnuson","orcid":"0000-0002-8824-6499","position":13,"is_corresponding":false},{"id":320874,"name":"Matthias Hebrok","orcid":"0000-0002-3833-8862","position":14,"is_corresponding":false},{"id":41041,"name":"Yuval Dor","orcid":"0000-0003-2456-2289","position":15,"is_corresponding":false},{"id":250525,"name":"Roland Stein","orcid":"0000-0001-9192-8661","position":16,"is_corresponding":false},{"id":250517,"name":"Jeeyeon Cha","orcid":"0000-0002-0312-2391","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T01:14:10.680991Z","pmid":"37606041","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":[]}