{"doi":"10.3389/fendo.2025.1695980","title":"TAS1R3 influences GTPase-dependent signaling in human islet β-cells","abstract":"Background: The taste receptor type 1 member 3 (TAS1R3), a G protein-coupled receptor (GPCR), is expressed in pancreatic islet β-cells where it may influence intracellular signaling pathways critical for β-cell function. Although TAS1R3 is known to couple to heterotrimeric G-proteins, its potential influence on small GTPases-key regulators of vesicle trafficking, cytoskeletal remodeling, and signal transduction-remains unexplored. Investigating how TAS1R3 modulates small GTPase activity could uncover mechanisms by which β cells regulate insulin secretion and adapt to metabolic cues. Objective: activation of small GTPases. Methods and results: We found that pharmacological TAS1R3 inhibition (lactisole) in human islets and a human β-cell line diminished glucose-stimulated insulin secretion, attenuated Src family tyrosine kinase signaling, and small GTPase Cdc42 activation. We excluded the requirement for the G protein Gαq/11 in TAS1R3 signaling by using the Gαq/11-specific YM-254890 inhibitor in β-cells. Notably, the significant reduction of TAS1R3 mRNA and protein levels in human type 2 diabetes pancreatic islets, which could be replicated in otherwise healthy cells exposed to diabetogenic stimuli, indicates that the TAS1R3 deficit may be a consequence of diabetogenic stimuli. Conclusion: Overall, our results suggest that TAS1R3 plays an essential role in GTPase signaling in islet β-cells adding to the growing list of proteins that play a vital role in islets as therapeutic targets in type 2 diabetes.","journal":"Frontiers in Endocrinology","year":2025,"id":554549,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"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":0.9651,"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":754933,"name":"Miwon Ahn","orcid":"0009-0000-5723-4447","position":1,"is_corresponding":false},{"id":754934,"name":"Eunjin Oh","orcid":"0009-0003-9437-0570","position":2,"is_corresponding":false},{"id":241714,"name":"Debbie C. Thurmond","orcid":"0000-0002-6303-4596","position":3,"is_corresponding":false},{"id":686587,"name":"Rajakrishnan Veluthakal","orcid":"0000-0002-4685-0647","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:54:50.112989Z","pmid":"41438300","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":[]}