{"doi":"10.1016/j.jbc.2025.108388","title":"Cardioprotective effect of genetic ablation of the G-protein-coupled receptor kinase GRK2 in adult pancreatic β-cells during high-fat diet","abstract":"Cardiovascular diseases are a major comorbidity factor in patients with type 2 diabetes and a leading cause of death among them. Yet, mechanistically, how impairment in pancreatic islets alters cardiac function under different metabolic states remains largely unknown. Here, we investigate the role of the G-protein-coupled receptor kinase 2 (GRK2) in regulating islet adaptations to an obesogenic diet and its impact on myocardial function. Using a novel inducible β-cell-specific GRK2 knockout mouse model (βGRK2KO), we establish that loss of adult β-cell GRK2 delays metabolic islet maladaptation, protecting the heart against obesity-induced cardiac dysfunction. βGRK2KO are more insulin-sensitive than control mice and have improved cardiac function and myocardial morphology. Thus, genetic ablation of GRK2 in adult β-cells during an obesogenic diet play a cardioprotective role. This study prompts a novel therapeutic window for GRK2 intervention strategies for diabetic patients prone to cardiac dysfunction.","journal":"Journal of Biological Chemistry","year":2025,"id":543343,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.96,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":707031,"name":"Chunsun Jiang","orcid":null,"position":1,"is_corresponding":false},{"id":1331811,"name":"Ran Hee Choi","orcid":"0000-0001-9002-2657","position":2,"is_corresponding":false},{"id":1433405,"name":"Taylor Morgan","orcid":null,"position":3,"is_corresponding":false},{"id":858387,"name":"Jeffrey Roman","orcid":null,"position":4,"is_corresponding":false},{"id":1308673,"name":"Lilly Underwood","orcid":null,"position":5,"is_corresponding":false},{"id":546883,"name":"Anna Maria Lucchese","orcid":"0000-0002-7160-1626","position":6,"is_corresponding":false},{"id":262440,"name":"Sarah Montgomery","orcid":"0000-0002-4189-5416","position":7,"is_corresponding":false},{"id":658642,"name":"Laurel A. Grisanti","orcid":"0000-0001-9780-1784","position":8,"is_corresponding":false},{"id":415494,"name":"Nicolai M. Doliba","orcid":"0000-0003-4598-9222","position":9,"is_corresponding":false},{"id":232413,"name":"William L. Holland","orcid":"0000-0001-9950-1435","position":10,"is_corresponding":false},{"id":380500,"name":"Priscila Y. Sato","orcid":"0000-0003-0512-7011","position":11,"is_corresponding":false},{"id":6504,"name":"Jonathan Snyder","orcid":"0000-0003-4664-8753","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T02:53:04.088079Z","pmid":"40054692","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":[]}