{"doi":"10.1172/jci173214","title":"SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes","abstract":"Pancreatic β cell dysfunction is a key feature of type 2 diabetes, and novel regulators of insulin secretion are desirable. Here, we report that succinate receptor 1 (SUCNR1) is expressed in β cells and is upregulated in hyperglycemic states in mice and humans. We found that succinate acted as a hormone-like metabolite and stimulated insulin secretion via a SUCNR1-Gq-PKC-dependent mechanism in human β cells. Mice with β cell-specific Sucnr1 deficiency exhibited impaired glucose tolerance and insulin secretion on a high-fat diet, indicating that SUCNR1 is essential for preserving insulin secretion in diet-induced insulin resistance. Patients with impaired glucose tolerance showed an enhanced nutrition-related succinate response, which correlates with the potentiation of insulin secretion during intravenous glucose administration. These data demonstrate that the succinate/SUCNR1 axis is activated by high glucose and identify a GPCR-mediated amplifying pathway for insulin secretion relevant to the hyperinsulinemia of prediabetic states.","journal":"Journal of Clinical Investigation","year":2024,"id":421591,"datarank":0.5101796072493234,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"self_citation_contribution":0.5101796072493234,"citation_network_contribution":0.0,"self_endowment_contribution":0.5101796072493234,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.953,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1214455,"name":"Brenno Astiarraga","orcid":"0000-0002-6654-7450","position":1,"is_corresponding":false},{"id":84118,"name":"Carlos Castaño","orcid":"0000-0003-1671-7826","position":2,"is_corresponding":false},{"id":1214456,"name":"Miriam Ejarque","orcid":"0000-0003-0545-9817","position":3,"is_corresponding":false},{"id":1214457,"name":"Maria Repollés-de-Dalmau","orcid":"0000-0003-1402-0611","position":4,"is_corresponding":false},{"id":908030,"name":"Iván Quesada","orcid":"0000-0002-9808-514X","position":5,"is_corresponding":false},{"id":1214458,"name":"Jordi Blanco","orcid":"0000-0001-8016-0984","position":6,"is_corresponding":false},{"id":1214459,"name":"Catalina Núñez‐Roa","orcid":"0000-0003-2764-5610","position":7,"is_corresponding":false},{"id":1214460,"name":"M‐Mar Rodríguez‐Peña","orcid":"0000-0003-2553-9769","position":8,"is_corresponding":false},{"id":1214461,"name":"Laia Martínez","orcid":"0000-0002-9350-0084","position":9,"is_corresponding":false},{"id":294804,"name":"Dario F. De Jesus","orcid":"0000-0001-8826-9095","position":10,"is_corresponding":false},{"id":1070564,"name":"Laura Marroquí","orcid":"0000-0003-2931-9317","position":11,"is_corresponding":false},{"id":1214462,"name":"Ramón Bosch","orcid":"0000-0003-4104-5515","position":12,"is_corresponding":false},{"id":1172213,"name":"Eduard Montanya","orcid":"0000-0003-2518-9076","position":13,"is_corresponding":false},{"id":1214463,"name":"Francesc X. Sureda","orcid":"0000-0002-7968-3929","position":14,"is_corresponding":false},{"id":481209,"name":"Andrea Tura","orcid":"0000-0003-3466-5900","position":15,"is_corresponding":false},{"id":285389,"name":"Andrea Mari","orcid":"0000-0002-1436-5591","position":16,"is_corresponding":false},{"id":664276,"name":"Rohit N. Kulkarni","orcid":null,"position":17,"is_corresponding":false},{"id":1214464,"name":"Joan Vendrell","orcid":"0000-0002-6994-6115","position":18,"is_corresponding":false},{"id":1214465,"name":"Sonia Fernández‐Veledo","orcid":"0000-0003-2906-3788","position":19,"is_corresponding":false},{"id":1214454,"name":"Joan Sabadell‐Basallote","orcid":"0000-0003-3608-1837","position":0,"is_corresponding":true}],"reference_count":102,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:57:41.370244Z","pmid":"38713514","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":[]}