{"doi":"10.7554/elife.88189.3","title":"Novel regulators of islet function identified from genetic variation in mouse islet Ca2+ oscillations","abstract":"Insufficient insulin secretion to meet metabolic demand results in diabetes. The intracellular flux of Ca 2+ into β-cells triggers insulin release. Since genetics strongly influences variation in islet secretory responses, we surveyed islet Ca 2+ dynamics in eight genetically diverse mouse strains. We found high strain variation in response to four conditions: (1) 8 mM glucose; (2) 8 mM glucose plus amino acids; (3) 8 mM glucose, amino acids, plus 10 nM glucose-dependent insulinotropic polypeptide (GIP); and (4) 2 mM glucose. These stimuli interrogate β-cell function, α- to β-cell signaling, and incretin responses. We then correlated components of the Ca 2+ waveforms to islet protein abundances in the same strains used for the Ca 2+ measurements. To focus on proteins relevant to human islet function, we identified human orthologues of correlated mouse proteins that are proximal to glycemic-associated single-nucleotide polymorphisms in human genome-wide association studies. Several orthologues have previously been shown to regulate insulin secretion (e.g. ABCC8, PCSK1, and GCK), supporting our mouse-to-human integration as a discovery platform. By integrating these data, we nominate novel regulators of islet Ca 2+ oscillations and insulin secretion with potential relevance for human islet function. We also provide a resource for identifying appropriate mouse strains in which to study these regulators.","journal":"eLife","year":2023,"id":367465,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.949,"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":471624,"name":"Lauren E. Clark","orcid":"0000-0002-0209-9716","position":1,"is_corresponding":false},{"id":861604,"name":"Brian S. Yandell","orcid":"0000-0002-8774-9377","position":2,"is_corresponding":false},{"id":321082,"name":"Kathryn L. Schueler","orcid":"0000-0003-4260-581X","position":3,"is_corresponding":false},{"id":704918,"name":"Shane P. Simonett","orcid":"0000-0002-9359-7808","position":4,"is_corresponding":false},{"id":516426,"name":"Donnie S. Stapleton","orcid":"0000-0002-7108-3718","position":5,"is_corresponding":false},{"id":860164,"name":"Kelly A. Mitok","orcid":"0000-0002-0167-3990","position":6,"is_corresponding":false},{"id":258194,"name":"Matthew J. Merrins","orcid":"0000-0003-1599-9227","position":7,"is_corresponding":false},{"id":321083,"name":"Mark P. Keller","orcid":"0000-0002-7405-5552","position":8,"is_corresponding":false},{"id":321086,"name":"Alan Attie","orcid":"0000-0002-0568-2261","position":9,"is_corresponding":false},{"id":607876,"name":"Christopher H. Emfinger","orcid":"0000-0002-9130-4194","position":0,"is_corresponding":true}],"reference_count":95,"raw_metadata":null,"created_at":"2026-07-19T01:15:12.215513Z","pmid":null,"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":[]}