{"doi":"10.1172/jci.insight.156378","title":"14-3-3ζ Constrains insulin secretion by regulating mitochondrial function in pancreatic β cells","abstract":"While critical for neurotransmitter synthesis, 14-3-3 proteins are often assumed to have redundant functions due to their ubiquitous expression, but despite this assumption, various 14-3-3 isoforms have been implicated in regulating metabolism. We previously reported contributions of 14-3-3ζ in β cell function, but these studies were performed in tumor-derived MIN6 cells and systemic KO mice. To further characterize the regulatory roles of 14-3-3ζ in β cell function, we generated β cell-specific 14-3-3ζ-KO mice. Although no effects on β cell mass were detected, potentiated glucose-stimulated insulin secretion (GSIS), mitochondrial function, and ATP synthesis were observed. Deletion of 14-3-3ζ also altered the β cell transcriptome, as genes associated with mitochondrial respiration and oxidative phosphorylation were upregulated. Acute 14-3-3 protein inhibition in mouse and human islets recapitulated the enhancements in GSIS and mitochondrial function, suggesting that 14-3-3ζ is the critical isoform in β cells. In dysfunctional db/db islets and human islets from type 2 diabetic donors, expression of Ywhaz/YWHAZ, the gene encoding 14-3-3ζ, was inversely associated with insulin secretion, and pan-14-3-3 protein inhibition led to enhanced GSIS and mitochondrial function. Taken together, this study demonstrates important regulatory functions of 14-3-3ζ in the regulation of β cell function and provides a deeper understanding of how insulin secretion is controlled in β cells.","journal":"JCI Insight","year":2022,"id":249247,"datarank":0.8735307134627733,"base_score":3.367295829986474,"endowment":3.367295829986474,"self_citation_contribution":0.5050943744979712,"citation_network_contribution":0.3684363389648021,"self_endowment_contribution":0.5050943744979712,"citer_contribution":0.3684363389648021,"corpus_percentile":null,"corpus_rank":null,"citation_count":28,"citer_count":23,"citers_with_citation_signal":19,"citers_with_endowment":19,"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":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":889400,"name":"Cheng Zhao","orcid":"0000-0003-0518-5924","position":1,"is_corresponding":false},{"id":889401,"name":"Ju Jing Tan","orcid":"0000-0003-3216-618X","position":2,"is_corresponding":false},{"id":889402,"name":"Anindya Ghosh","orcid":"0000-0002-8432-5288","position":3,"is_corresponding":false},{"id":737385,"name":"S. Campbell","orcid":"0000-0001-6788-3002","position":4,"is_corresponding":false},{"id":889935,"name":"Evgenia Fadzeyeva","orcid":null,"position":5,"is_corresponding":false},{"id":889936,"name":"Frédéric Paré","orcid":null,"position":6,"is_corresponding":false},{"id":889937,"name":"Siew Siew Pan","orcid":null,"position":7,"is_corresponding":false},{"id":889403,"name":"Maria Galipeau","orcid":"0000-0002-8639-8253","position":8,"is_corresponding":false},{"id":260255,"name":"Julia Ast","orcid":"0000-0002-0039-4762","position":9,"is_corresponding":false},{"id":260273,"name":"Johannes Broichhagen","orcid":"0000-0003-3084-6595","position":10,"is_corresponding":false},{"id":236999,"name":"David J. Hodson","orcid":"0000-0002-8641-8568","position":11,"is_corresponding":false},{"id":301224,"name":"Erin E. Mulvihill","orcid":"0000-0002-3981-0241","position":12,"is_corresponding":false},{"id":889404,"name":"Sophie Petropoulos","orcid":"0000-0003-2293-8238","position":13,"is_corresponding":false},{"id":889405,"name":"Gareth E. Lim","orcid":"0000-0003-3850-3757","position":14,"is_corresponding":false},{"id":889934,"name":"Yves Mugabo","orcid":null,"position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:24:19.356023Z","pmid":"35298439","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":[]}