{"doi":"10.1016/j.jbc.2025.108187","title":"Pancreatic expression of CPT1A is essential for whole body glucose homeostasis by supporting glucose-stimulated insulin secretion","abstract":"Pancreatic islet β-cells express the Cpt1a gene, which encodes the enzyme carnitine palmitoyltransferase 1A (CPT1A), an enzyme that facilitates entry of long-chain fatty acids into the mitochondria. Because fatty acids are required for glucose-stimulated insulin secretion, we tested the hypothesis that CPT1A is essential to support islet β-cell function and mass. In this study, we describe genetic deletion of Cpt1a in pancreatic tissue (Cpt1a Pdx1−/− ) using C57BL/6J mice. Islet morphology, β-cell transcription factor abundance, islet ATP levels, glucose transporter 2 abundance, and expression of the dedifferentiation marker ALDH1A3 were analyzed by immunofluorescent staining. Glucose and insulin tolerance were assessed to investigate the metabolic status of genetic reductions in Cpt1a . Glucose-stimulated insulin secretion was evaluated in vivo and in isolated islets ex vivo by perifusion. Pancreatic deletion of Cpt1a reduced glucose tolerance but did not alter insulin sensitivity. Glucose-stimulated insulin secretion was reduced both in vivo and in islets isolated from Cpt1a Pdx1−/− mice relative to control islets. Pancreatic islets from Cpt1a Pdx1−/− mice displayed elevations in ALDH1A3, a marker of dedifferentiation, but no reduction in nuclear abundance of the β-cell transcription factors MafA and Nkx6.1 or the GLUT2 glucose transporter. However, intracellular ATP abundance was markedly decreased in islets isolated from Cpt1a Pdx1−/− relative to littermate control mice. We conclude that there is an important physiological role for pancreatic CPT1A to maintain whole body glucose homeostasis by supporting glucose-stimulated insulin secretion and maintaining intracellular ATP levels in male mice.","journal":"Journal of Biological Chemistry","year":2025,"id":530913,"datarank":0.25578581134013834,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.014370124475023255,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.014370124475023255,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":3,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE262423"]},"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":1411243,"name":"Caroline R Cothern","orcid":null,"position":1,"is_corresponding":false},{"id":419208,"name":"Heidi M. Batdorf","orcid":null,"position":2,"is_corresponding":false},{"id":1282934,"name":"M. Fontenot","orcid":null,"position":3,"is_corresponding":false},{"id":316544,"name":"Thomas M. Martin","orcid":"0000-0002-1671-6498","position":4,"is_corresponding":false},{"id":1038484,"name":"Maria Iftesum","orcid":"0000-0002-8594-3678","position":5,"is_corresponding":false},{"id":428306,"name":"Manas Ranjan Gartia","orcid":"0000-0001-6243-6780","position":6,"is_corresponding":false},{"id":289078,"name":"Robert C. Noland","orcid":"0000-0001-5543-3450","position":7,"is_corresponding":false},{"id":418286,"name":"David H. Burk","orcid":"0000-0002-6487-0174","position":8,"is_corresponding":false},{"id":250669,"name":"Sujoy Ghosh","orcid":"0000-0002-7601-165X","position":9,"is_corresponding":false},{"id":418292,"name":"Susan J. Burke","orcid":"0000-0003-2571-4416","position":10,"is_corresponding":false},{"id":1411242,"name":"Maggie P. Ducote","orcid":null,"position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T02:51:10.077559Z","pmid":"39814231","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":[]}