{"doi":"10.3389/fendo.2025.1630979","title":"Pdgfrα deficiency in islet β-cells up-regulates apoptosis of beta-cells and disturbs glucose metabolism in B6 mice","abstract":"Introduction: Pancreatic β-cell dysfunction is a key contributor to the development of Type 2 Diabetes. The platelet-derived growth factor receptor α (PDGFRα) is known to play a crucial role in β-cell proliferation and expansion. However, its specific role in β-cell function and glucose metabolism remains unclear. This study aimed to investigate the effects of Pdgfrα deficiency on islet β-cell function and overall glucose metabolism. Methods: ) and assessed their metabolic function under both normal and high-fat diet conditions. Various parameters were measured, including body weight, body fat composition, glucose metabolism, insulin content, and β-cell apoptosis. Additionally, we conducted mechanistic analyses to understand the signaling pathways involved. Results: Pdgfrα-deficient mice exhibited significantly greater weight gain and increased body fat compared to controls. These mice also showed impaired glucose metabolism, reduced insulin content in β-cells, and increased β-cell apoptosis. Mechanistic studies revealed that Pdgfrα deletion led to suppression of Atf5 expression via downregulation of the PI3K pathway. This suppression resulted in enhanced β-cell apoptosis. Furthermore, Atf5 was found to regulate the expression of Gadd45b, Bcl2, and aminoacyl-tRNA synthetases, which are involved in insulin biosynthesis and glucose metabolism. Discussion: Our findings demonstrate that PDGFRα plays a critical role in maintaining β-cell function and glucose homeostasis. Loss of PDGFRα impairs β-cell survival and insulin production, likely through the PI3K-Atf5 axis. These insights suggest that targeting β-cell apoptotic pathways, particularly involving Atf5 and its downstream effectors, may offer promising avenues for the prevention and treatment of Type 2 Diabetes.","journal":"Frontiers in Endocrinology","year":2025,"id":579385,"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":0.9606,"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":691907,"name":"Yanpeng Xing","orcid":null,"position":1,"is_corresponding":false},{"id":1077049,"name":"Pai Wang","orcid":"0000-0002-7829-8519","position":2,"is_corresponding":false},{"id":326596,"name":"Jianlei Gu","orcid":"0000-0002-9337-5017","position":3,"is_corresponding":false},{"id":691333,"name":"Jian Peng","orcid":"0000-0003-0991-3896","position":4,"is_corresponding":false},{"id":691330,"name":"Juan Huang","orcid":"0009-0009-6846-2678","position":5,"is_corresponding":false},{"id":344635,"name":"James A. Pearson","orcid":"0000-0002-2867-2269","position":6,"is_corresponding":false},{"id":691908,"name":"Youjia Hu","orcid":null,"position":7,"is_corresponding":false},{"id":2737,"name":"Luca Pinello","orcid":"0000-0003-1195-9607","position":8,"is_corresponding":false},{"id":344636,"name":"F. Susan Wong","orcid":"0000-0002-2812-8845","position":9,"is_corresponding":false},{"id":460909,"name":"Li Wen","orcid":"0000-0002-8620-5757","position":10,"is_corresponding":false},{"id":691334,"name":"Luyao Zhang","orcid":"0000-0001-9408-9496","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T02:58:30.282164Z","pmid":"41234234","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":[]}