{"doi":"10.1016/j.celrep.2023.112500","title":"Vitamin K-dependent carboxylation regulates Ca2+ flux and adaptation to metabolic stress in β cells","abstract":"Vitamin K is a micronutrient necessary for γ-carboxylation of glutamic acids. This post-translational modification occurs in the endoplasmic reticulum (ER) and affects secreted proteins. Recent clinical studies implicate vitamin K in the pathophysiology of diabetes, but the underlying molecular mechanism remains unknown. Here, we show that mouse β cells lacking γ-carboxylation fail to adapt their insulin secretion in the context of age-related insulin resistance or diet-induced β cell stress. In human islets, γ-carboxylase expression positively correlates with improved insulin secretion in response to glucose. We identify endoplasmic reticulum Gla protein (ERGP) as a γ-carboxylated ER-resident Ca 2+ -binding protein expressed in β cells. Mechanistically, γ-carboxylation of ERGP protects cells against Ca 2+ overfilling by diminishing STIM1 and Orai1 interaction and restraining store-operated Ca 2+ entry. These results reveal a critical role of vitamin K-dependent carboxylation in regulation of Ca 2+ flux in β cells and in their capacity to adapt to metabolic stress.","journal":"Cell Reports","year":2023,"id":328908,"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":0.9523,"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":353757,"name":"Kevin Guo","orcid":"0000-0002-5893-2164","position":1,"is_corresponding":false},{"id":1003070,"name":"Jessica Bonneau","orcid":"0000-0002-6751-1150","position":2,"is_corresponding":false},{"id":582311,"name":"Denis Faubert","orcid":"0000-0001-9550-4495","position":3,"is_corresponding":false},{"id":1003404,"name":"Florian Gioanni","orcid":null,"position":4,"is_corresponding":false},{"id":828580,"name":"Alexis Vivoli","orcid":"0000-0002-6056-9632","position":5,"is_corresponding":false},{"id":1003071,"name":"Sarah M. Muir","orcid":"0000-0002-7082-7199","position":6,"is_corresponding":false},{"id":1003072,"name":"Soraya Hezzaz","orcid":"0009-0009-5984-2767","position":7,"is_corresponding":false},{"id":576873,"name":"Vincent Poitout","orcid":"0000-0002-6555-5053","position":8,"is_corresponding":false},{"id":497947,"name":"Mathieu Ferron","orcid":"0000-0002-5858-2686","position":9,"is_corresponding":false},{"id":1003069,"name":"Julie Lacombe","orcid":"0000-0002-1046-9908","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-19T01:08:56.940647Z","pmid":"37171959","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":[]}