{"doi":"10.2337/db23-0483","title":"RFX6 Maintains Gene Expression and Function of Adult Human Islet α-Cells","abstract":"Mutations in the gene encoding the transcription factor regulatory factor X-box binding 6 (RFX6) are associated with human diabetes. Within pancreatic islets, RFX6 expression is most abundant in islet α-cells, and α-cell RFX6 expression is altered in diabetes. However, the roles of RFX6 in regulating gene expression, glucagon output, and other crucial human adult α-cell functions are not yet understood. We developed a method for selective genetic targeting of human α-cells and assessed RFX6-dependent α-cell function. RFX6 suppression with RNA interference led to impaired α-cell exocytosis and dysregulated glucagon secretion in vitro and in vivo. By contrast, these phenotypes were not observed with RFX6 suppression across all islet cells. Transcriptomics in α-cells revealed RFX6-dependent expression of genes governing nutrient sensing, hormone processing, and secretion, with some of these exclusively expressed in human α-cells. Mapping of RFX6 DNA-binding sites in primary human islet cells identified a subset of direct RFX6 target genes. Together, these data unveil RFX6-dependent genetic targets and mechanisms crucial for regulating adult human α-cell function.","journal":"Diabetes","year":2023,"id":348847,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9564,"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":881214,"name":"Mollie F. Qian","orcid":"0000-0001-7536-9054","position":1,"is_corresponding":false},{"id":467427,"name":"Krissie Tellez","orcid":"0000-0002-8892-216X","position":2,"is_corresponding":false},{"id":238645,"name":"Austin Bautista","orcid":null,"position":3,"is_corresponding":false},{"id":467426,"name":"Romina J. Bevacqua","orcid":"0000-0002-3903-6508","position":4,"is_corresponding":false},{"id":467423,"name":"Xueying Gu","orcid":"0000-0001-6572-6089","position":5,"is_corresponding":false},{"id":74020,"name":"Yan Hang","orcid":"0000-0002-5166-2480","position":6,"is_corresponding":false},{"id":1091577,"name":"Martin Neukam","orcid":"0000-0002-5743-9204","position":7,"is_corresponding":false},{"id":661976,"name":"Weichen Zhao","orcid":"0000-0003-4838-7016","position":8,"is_corresponding":false},{"id":74126,"name":"Charles Chang","orcid":"0000-0003-0710-3080","position":9,"is_corresponding":false},{"id":7384,"name":"Patrick E. MacDonald","orcid":"0000-0002-5439-6288","position":10,"is_corresponding":false},{"id":44518,"name":"Seung K. Kim","orcid":"0000-0001-6135-7810","position":11,"is_corresponding":false},{"id":1092084,"name":"Vy M. N. Coykendall","orcid":null,"position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T01:12:10.335697Z","pmid":"38064570","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":[]}