{"doi":"10.1016/j.jbc.2021.100482","title":"Disrupted glucose homeostasis and skeletal-muscle-specific glucose uptake in an exocyst knockout mouse model","abstract":"Skeletal muscle is responsible for the majority of glucose disposal following meals, and this is achieved by insulin-mediated trafficking of glucose transporter type 4 (GLUT4) to the cell membrane. The eight-protein exocyst trafficking complex facilitates targeted docking of membrane-bound vesicles, a process underlying the regulated delivery of fuel transporters. We previously demonstrated the role of exocyst subunit EXOC5 in insulin-stimulated GLUT4 exocytosis and glucose uptake in cultured rat skeletal myoblasts. However, the in vivo role of EXOC5 in skeletal muscle remains unclear. Using mice with inducible, skeletal-muscle-specific knockout of exocyst subunit EXOC5 (Exoc5-SMKO), we examined how muscle-specific disruption of the exocyst would affect glucose homeostasis in vivo. We found that both male and female Exoc5-SMKO mice displayed elevated fasting glucose levels. Additionally, male Exoc5-SMKO mice had impaired glucose tolerance and lower serum insulin levels. Using indirect calorimetry, we observed that male Exoc5-SMKO mice have a reduced respiratory exchange ratio during the light period and lower energy expenditure. Using the hyperinsulinemic-euglycemic clamp method, we further showed that insulin-stimulated skeletal muscle glucose uptake is reduced in Exoc5-SMKO males compared with wild-type controls. Overall, our findings indicate that EXOC5 and the exocyst are necessary for insulin-stimulated glucose uptake in skeletal muscle and regulate glucose homeostasis in vivo.","journal":"Journal of Biological Chemistry","year":2021,"id":176157,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":718696,"name":"Madison Young","orcid":null,"position":1,"is_corresponding":false},{"id":718697,"name":"Nicole Nakamura","orcid":null,"position":2,"is_corresponding":false},{"id":718698,"name":"Herena Y. Ha","orcid":null,"position":3,"is_corresponding":false},{"id":718699,"name":"Lamar Carter","orcid":null,"position":4,"is_corresponding":false},{"id":302888,"name":"Matthew W. Pitts","orcid":"0000-0002-0994-7466","position":5,"is_corresponding":false},{"id":302887,"name":"Daniel J. Torres","orcid":"0000-0002-4451-712X","position":6,"is_corresponding":false},{"id":210939,"name":"Hye Lim Noh","orcid":null,"position":7,"is_corresponding":false},{"id":210941,"name":"Sujin Suk","orcid":null,"position":8,"is_corresponding":false},{"id":245309,"name":"Jason K. Kim","orcid":"0000-0002-7185-042X","position":9,"is_corresponding":false},{"id":718156,"name":"Noémi Polgár","orcid":"0000-0002-8400-162X","position":10,"is_corresponding":false},{"id":718155,"name":"B. Fujimoto","orcid":"0000-0002-8341-1571","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-18T23:47:19.591542Z","pmid":"33647317","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":[]}