{"doi":"10.1038/s42003-025-08787-1","title":"Pancreatic β-cell FFA2 deficiency suppresses multiple low dose streptozotocin induced diabetes in male mice","abstract":"Reduced enrichment of short-chain fatty acid (SCFA)-producing pathways in the gut microbiome (GM) and SCFA levels are associated with increased risk of type 1 diabetes (T1D). Free fatty acid receptor 2 (FFA2), an SCFA receptor on pancreatic β-cells, mediates GM and β-cell crosstalk. Here, we examine its T1D-specific role in male mice, using a novel tamoxifen-inducible adult-onset β-cell FFA2 knockout (FFA2 βKO) mouse model and its controls (cre and flox), treated with multiple low-dose streptozotocin (MLDS). FFA2 βKO mice show significantly lower diabetes incidence compared to control mice (57% vs 100%). Early in the MLDS insult (7th day), FFA2 βKO mice show significantly lower β-cell apoptosis and higher β-cell mass, persisting up to 43 days. Mechanistically, we observed higher SOCS1/3 expression and reduced T1-IFN signaling in FFA2 βKO islets. Our data suggest that β-cell FFA2 modulates early islet apoptosis, likely via the T1-IFN-SOCS1/3 pathway and may be a pharmacological target for slowing T1D progression. The short-chain fatty acid receptor FFA2 plays a role in modulating beta cell responses to multiple low-dose streptozotocin via T1-IFN signaling. This suggests that FFA2 could be a therapeutic target in type 1 diabetes.","journal":"Communications Biology","year":2025,"id":576397,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"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":416410,"name":"Prabhakaran Kumar","orcid":"0000-0002-0657-6938","position":1,"is_corresponding":false},{"id":1485298,"name":"Sophia R. Chang Stauffer","orcid":null,"position":2,"is_corresponding":false},{"id":1485299,"name":"Husena M. Electricwala","orcid":null,"position":3,"is_corresponding":false},{"id":416411,"name":"Bellur S. Prabhakar","orcid":"0000-0001-9815-9850","position":4,"is_corresponding":false},{"id":1343440,"name":"Irene Corona‐Avila","orcid":null,"position":5,"is_corresponding":false},{"id":1120485,"name":"Nupur Pandya","orcid":null,"position":6,"is_corresponding":false},{"id":280649,"name":"Brian T. Layden","orcid":"0000-0003-2176-5654","position":7,"is_corresponding":false},{"id":475250,"name":"Medha Priyadarshini","orcid":"0000-0003-2972-2528","position":8,"is_corresponding":false},{"id":751144,"name":"Kai Xu","orcid":"0000-0001-7792-8235","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-19T02:57:56.636458Z","pmid":"41028169","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":[]}