{"doi":"10.1016/j.celrep.2020.107623","title":"Glucose Response by Stem Cell-Derived β Cells In Vitro Is Inhibited by a Bottleneck in Glycolysis","abstract":"Stem cell-derived β (SC-β) cells could provide unlimited human β cells toward a curative diabetes treatment. Differentiation of SC-β cells yields transplantable islets that secrete insulin in response to glucose challenges. Following transplantation into mice, SC-β cell function is comparable to human islets, but the magnitude and consistency of response in vitro are less robust than observed in cadaveric islets. Here, we profile metabolism of SC-β cells and islets to quantify their capacity to sense glucose and identify reduced anaplerotic cycling in the mitochondria as the cause of reduced glucose-stimulated insulin secretion in SC-β cells. This activity can be rescued by challenging SC-β cells with intermediate metabolites from the TCA cycle and late but not early glycolysis, downstream of the enzymes glyceraldehyde 3-phosphate dehydrogenase and phosphoglycerate kinase. Bypassing this metabolic bottleneck results in a robust, bi-phasic insulin release in vitro that is identical in magnitude to functionally mature human islets.","journal":"Cell Reports","year":2020,"id":52132,"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":140,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"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":258188,"name":"Tiago C. Alves","orcid":"0000-0002-4431-5886","position":1,"is_corresponding":false},{"id":262793,"name":"Aharon Helman","orcid":"0000-0002-3415-154X","position":2,"is_corresponding":false},{"id":262794,"name":"Jonathan C. Chen","orcid":"0000-0003-4346-0501","position":3,"is_corresponding":false},{"id":262795,"name":"Jennifer Hyoje-Ryu Kenty","orcid":"0000-0003-0974-9643","position":4,"is_corresponding":false},{"id":257018,"name":"Rebecca Cardone","orcid":null,"position":5,"is_corresponding":false},{"id":32147,"name":"David R. Liu","orcid":"0000-0002-9943-7557","position":6,"is_corresponding":false},{"id":254925,"name":"Richard G. Kibbey","orcid":"0000-0001-6768-3473","position":7,"is_corresponding":false},{"id":45690,"name":"Douglas A. Melton","orcid":"0000-0002-1623-5504","position":8,"is_corresponding":false},{"id":265177,"name":"Jeffrey C. Davis","orcid":null,"position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-18T20:42:26.843314Z","pmid":"32402282","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":[]}