{"doi":"10.1126/sciadv.abn3773","title":"14-3-3-zeta mediates GLP-1 receptor agonist action to alter α cell proglucagon processing","abstract":"Recent studies demonstrate that α cells contribute to glucose-stimulated insulin secretion (GSIS). Glucagon-like peptide-1 receptor (GLP-1R) agonists potently potentiate GSIS, making these drugs useful for diabetes treatment. However, the role of α and β cell paracrine interactions in the effects of GLP-1R agonists is undefined. We previously found that increased β cell GLP-1R signaling activates α cell GLP-1 expression. Here, we characterized the bidirectional paracrine cross-talk by which α and β cells communicate to mediate the effects of the GLP-1R agonist, liraglutide. We find that the effect of liraglutide to enhance GSIS is blunted by α cell ablation in male mice. Furthermore, the effect of β cell GLP-1R signaling to activate α cell GLP-1 is mediated by a secreted protein factor that is regulated by the signaling protein, 14-3-3-zeta, in mouse and human islets. These data refine our understanding of GLP-1 pharmacology and identify 14-3-3-zeta as a potential target to enhance α cell GLP-1 production.","journal":"Science Advances","year":2022,"id":272979,"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":0.9514,"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":659617,"name":"Daryl J. Phuong","orcid":"0000-0003-4049-8694","position":1,"is_corresponding":false},{"id":659615,"name":"Isaac S. Lee","orcid":"0000-0003-1371-8364","position":2,"is_corresponding":false},{"id":368724,"name":"Mridusmita Saikia","orcid":"0000-0002-5848-3303","position":3,"is_corresponding":false},{"id":939930,"name":"Lisa Weikert","orcid":"0000-0003-0371-372X","position":4,"is_corresponding":false},{"id":940501,"name":"Samantha Fountain","orcid":null,"position":5,"is_corresponding":false},{"id":511619,"name":"Elizabeth T. Anderson","orcid":"0000-0003-1795-8269","position":6,"is_corresponding":false},{"id":299431,"name":"Qin Fu","orcid":"0000-0003-4944-772X","position":7,"is_corresponding":false},{"id":233145,"name":"Sheng Zhang","orcid":"0000-0001-8206-1007","position":8,"is_corresponding":false},{"id":63186,"name":"Kyle W. Sloop","orcid":"0000-0001-6748-9929","position":9,"is_corresponding":false},{"id":295098,"name":"Bethany P. Cummings","orcid":"0000-0002-0610-9870","position":10,"is_corresponding":false},{"id":295095,"name":"Marlena M. Holter","orcid":"0000-0002-1748-5409","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T00:27:52.048702Z","pmid":"35867787","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":[]}