{"doi":"10.1016/j.molmet.2023.101769","title":"Raptor levels are critical for β-cell adaptation to a high-fat diet in male mice","abstract":"OBJECTIVE: The essential role of raptor/mTORC1 signaling in β-cell survival and insulin processing has been recently demonstrated using raptor knock-out models. Our aim was to evaluate the role of mTORC1 function in adaptation of β-cells to insulin resistant state. METHOD: ) to assess whether reduced mTORC1 function is critical for β-cell function in normal conditions or during β-cell adaptation to high-fat diet (HFD). RESULTS: Deletion of a raptor allele in β-cells showed no differences at the metabolic level, islets morphology, or β-cell function in mice fed regular chow. Surprisingly, deletion of only one allele of raptor increases apoptosis without altering proliferation rate and is sufficient to impair insulin secretion when fed a HFD. This is accompanied by reduced levels of critical β-cell genes like Ins1, MafA, Ucn3, Glut2, Glp1r, and specially PDX1 suggesting an improper β-cell adaptation to HFD. CONCLUSION: This study identifies that raptor levels play a key role in maintaining PDX1 levels and β-cell function during the adaptation of β-cell to HFD. Finally, we identified that Raptor levels regulate PDX1 levels and β-cell function during β-cell adaptation to HFD by reduction of the mTORC1-mediated negative feedback and activation of the AKT/FOXA2/PDX1 axis. We suggest that Raptor levels are critical to maintaining PDX1 levels and β-cell function in conditions of insulin resistance in male mice.","journal":"Molecular Metabolism","year":2023,"id":371367,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9426,"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":709977,"name":"Ruy A. Louzada","orcid":"0000-0003-1789-4234","position":1,"is_corresponding":false},{"id":475617,"name":"João Pedro Werneck‐de‐Castro","orcid":"0000-0001-9242-7930","position":2,"is_corresponding":false},{"id":1129234,"name":"Camila Lubaczeuski","orcid":"0000-0001-6882-7686","position":3,"is_corresponding":false},{"id":7357,"name":"Joana Almaça","orcid":"0000-0002-9316-712X","position":4,"is_corresponding":false},{"id":1130996,"name":"Markus A. Rüegg","orcid":"0000-0002-4974-9384","position":5,"is_corresponding":false},{"id":1130997,"name":"Michael N. Hall","orcid":"0000-0002-2998-0757","position":6,"is_corresponding":false},{"id":709981,"name":"Gil Leibowitz","orcid":"0000-0002-9699-6353","position":7,"is_corresponding":false},{"id":464949,"name":"Ernesto Bernal‐Mizrachi","orcid":"0000-0001-9997-3301","position":8,"is_corresponding":false},{"id":709978,"name":"Manuel Blandino-Rosano","orcid":"0000-0002-1712-8233","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T01:15:45.330525Z","pmid":"37423392","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":[]}