{"doi":"10.1038/s42003-020-01226-3","title":"L-Arginine prevents cereblon-mediated ubiquitination of glucokinase and stimulates glucose-6-phosphate production in pancreatic β-cells","abstract":"Abstract We sought to determine a mechanism by which L -arginine increases glucose-stimulated insulin secretion (GSIS) in β-cells by finding a protein with affinity to L -arginine using arginine-immobilized magnetic nanobeads technology. Glucokinase (GCK), the key regulator of GSIS and a disease-causing gene of maturity-onset diabetes of the young type 2 (MODY2), was found to bind L -arginine. L -Arginine stimulated production of glucose-6-phosphate (G6P) and induced insulin secretion. We analyzed glucokinase mutants and identified three glutamate residues that mediate binding to L -arginine. One MODY2 patient with GCK E442* demonstrated lower C-peptide-to-glucose ratio after arginine administration. In β-cell line, GCK E442* reduced L -arginine-induced insulin secretion compared with GCK WT . In addition, we elucidated that the binding of arginine protects glucokinase from degradation by E3 ubiquitin ligase cereblon mediated ubiquitination. We conclude that L -arginine induces insulin secretion by increasing G6P production by glucokinase through direct stimulation and by prevention of degradation.","journal":"Communications Biology","year":2020,"id":76971,"datarank":0.8610082442887952,"base_score":3.044522437723423,"endowment":3.044522437723423,"self_citation_contribution":0.4566783656585135,"citation_network_contribution":0.4043298786302817,"self_endowment_contribution":0.4566783656585135,"citer_contribution":0.4043298786302817,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":14,"citers_with_citation_signal":11,"citers_with_endowment":11,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9638,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":403138,"name":"Yukio Horikawa","orcid":null,"position":1,"is_corresponding":false},{"id":403139,"name":"Mayumi Enya","orcid":null,"position":2,"is_corresponding":false},{"id":401471,"name":"Jun Takeda","orcid":"0000-0002-6195-8971","position":3,"is_corresponding":false},{"id":401472,"name":"Yoichi Imai","orcid":"0000-0002-2938-6133","position":4,"is_corresponding":false},{"id":401473,"name":"Yumi Imai","orcid":"0000-0001-5046-4223","position":5,"is_corresponding":false},{"id":401474,"name":"Hiroshi Handa","orcid":"0000-0001-6656-9521","position":6,"is_corresponding":false},{"id":401475,"name":"Takeshi Imai","orcid":"0000-0002-9503-7353","position":7,"is_corresponding":false},{"id":401470,"name":"Jaeyong Cho","orcid":"0000-0001-7858-4382","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T21:48:50.085103Z","pmid":"32901087","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":[]}