{"doi":"10.1172/jci165208","title":"Nutrient regulation of the islet epigenome controls adaptive insulin secretion","abstract":"Adaptation of the islet β cell insulin-secretory response to changing insulin demand is critical for blood glucose homeostasis, yet the mechanisms underlying this adaptation are unknown. Here, we have shown that nutrient-stimulated histone acetylation plays a key role in adapting insulin secretion through regulation of genes involved in β cell nutrient sensing and metabolism. Nutrient regulation of the epigenome occurred at sites occupied by the chromatin-modifying enzyme lysine-specific demethylase 1 (Lsd1) in islets. β Cell-specific deletion of Lsd1 led to insulin hypersecretion, aberrant expression of nutrient-response genes, and histone hyperacetylation. Islets from mice adapted to chronically increased insulin demand exhibited shared epigenetic and transcriptional changes. Moreover, we found that genetic variants associated with type 2 diabetes were enriched at LSD1-bound sites in human islets, suggesting that interpretation of nutrient signals is genetically determined and clinically relevant. Overall, these studies revealed that adaptive insulin secretion involves Lsd1-mediated coupling of nutrient state to regulation of the islet epigenome.","journal":"Journal of Clinical Investigation","year":2023,"id":332228,"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":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9474,"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":1058968,"name":"Fenfen Liu","orcid":null,"position":1,"is_corresponding":false},{"id":324886,"name":"Austin R. Harrington","orcid":null,"position":2,"is_corresponding":false},{"id":730034,"name":"Johanna Y. Fleischman","orcid":"0000-0002-5491-4110","position":3,"is_corresponding":false},{"id":233751,"name":"Martina Wallace","orcid":"0000-0001-8272-5678","position":4,"is_corresponding":false},{"id":587345,"name":"Francesca Mulas","orcid":null,"position":5,"is_corresponding":false},{"id":986161,"name":"Medhavi Mallick","orcid":null,"position":6,"is_corresponding":false},{"id":324883,"name":"Nicholas K. Vinckier","orcid":null,"position":7,"is_corresponding":false},{"id":1058969,"name":"Benjamin R. Cross","orcid":null,"position":8,"is_corresponding":false},{"id":23921,"name":"Joshua Chiou","orcid":"0000-0002-4618-0647","position":9,"is_corresponding":false},{"id":323898,"name":"Nisha Patel","orcid":"0000-0002-6316-1800","position":10,"is_corresponding":false},{"id":624623,"name":"Yinghui Sui","orcid":null,"position":11,"is_corresponding":false},{"id":23916,"name":"Carolyn McGrail","orcid":null,"position":12,"is_corresponding":false},{"id":809182,"name":"Yesl Jun","orcid":"0000-0002-7598-9226","position":13,"is_corresponding":false},{"id":23911,"name":"Gaowei Wang","orcid":null,"position":14,"is_corresponding":false},{"id":324889,"name":"Ulupi S. Jhala","orcid":null,"position":15,"is_corresponding":false},{"id":112215,"name":"Roland Schüle","orcid":"0000-0001-8147-634X","position":16,"is_corresponding":false},{"id":242295,"name":"Orian S. Shirihai","orcid":"0000-0001-8466-3431","position":17,"is_corresponding":false},{"id":7355,"name":"Mark O. Huising","orcid":"0000-0002-6594-2205","position":18,"is_corresponding":false},{"id":16068,"name":"Kyle J. Gaulton","orcid":"0000-0003-1318-7161","position":19,"is_corresponding":false},{"id":229039,"name":"Christian M. Metallo","orcid":"0000-0003-2404-3040","position":20,"is_corresponding":false},{"id":7364,"name":"Maike Sander","orcid":"0000-0001-5308-7785","position":21,"is_corresponding":false},{"id":324887,"name":"Matthew Wortham","orcid":null,"position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-19T01:09:30.139849Z","pmid":"36821378","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":[]}