2024
Glucose Regulation of β-Cell KATP Channels: It Is Time for a New Model!
Merrins M, Kibbey R. Glucose Regulation of β-Cell KATP Channels: It Is Time for a New Model! Diabetes 2024, 73: 856-863. PMID: 38768366, PMCID: PMC11109790, DOI: 10.2337/dbi23-0032.Peer-Reviewed Original ResearchConceptsB-cell metabolismInsulin secretionEfficiency of mitochondrial ATP productionModel of glucose-stimulated insulin secretionGlucose-stimulated insulin secretionMitochondrial ATP productionNADPH productionGenetic evidenceInitial insulin secretionATP productionGlycolytic enzymesOXPHOSPyruvate kinaseATP/ADP ratioHealthy B cellsKATP channel closureB cellsDiabetes pathophysiologyGlycolysisStoichiometric yieldKATP channelsBioenergeticsATP/ADPMembrane depolarizationMetabolism
2022
Citrullination of glucokinase is linked to autoimmune diabetes
Yang ML, Horstman S, Gee R, Guyer P, Lam TT, Kanyo J, Perdigoto AL, Speake C, Greenbaum CJ, Callebaut A, Overbergh L, Kibbey RG, Herold KC, James EA, Mamula MJ. Citrullination of glucokinase is linked to autoimmune diabetes. Nature Communications 2022, 13: 1870. PMID: 35388005, PMCID: PMC8986778, DOI: 10.1038/s41467-022-29512-0.Peer-Reviewed Original ResearchConceptsGlucose-stimulated insulin secretionResult of inflammationType 1 diabetesBeta-cell metabolismPancreatic beta cellsAutoimmune diabetesNOD miceAutoreactive CD4Inflammatory cytokinesAutoimmune biomarkersInsulin secretionT cellsBeta cellsType 1InflammationBiologic activityReactive oxygen speciesDiabetesPost-translational modificationsDiabetes biomarkersGlycogen synthesisBiomarkersCitrullinationGlucokinaseOxygen species
2020
Glucose Response by Stem Cell-Derived β Cells In Vitro Is Inhibited by a Bottleneck in Glycolysis
Davis JC, Alves TC, Helman A, Chen JC, Kenty JH, Cardone RL, Liu DR, Kibbey RG, Melton DA. Glucose Response by Stem Cell-Derived β Cells In Vitro Is Inhibited by a Bottleneck in Glycolysis. Cell Reports 2020, 31: 107623. PMID: 32402282, PMCID: PMC7433758, DOI: 10.1016/j.celrep.2020.107623.Peer-Reviewed Original ResearchConceptsSC-β cellsΒ-cellsHuman isletsReduced glucose-stimulated insulin secretionGlucose-stimulated insulin secretionStem cell-derived β cellsHuman β-cellsEnzyme glyceraldehydeTCA cycleGlucose challengeInsulin secretionInsulin releaseDiabetes treatmentGlucose responseCadaveric isletsBottleneck resultsEarly glycolysisTransplantable isletsCell functionIsletsIntermediate metabolitesConsistency of responsesGlycolysisCellsKinase
2019
Mitochondrial Proton Leak Regulated by Cyclophilin D Elevates Insulin Secretion in Islets at Nonstimulatory Glucose Levels
Taddeo EP, Alsabeeh N, Baghdasarian S, Wikstrom JD, Ritou E, Sereda S, Erion K, Li J, Stiles L, Abdulla M, Swanson Z, Wilhelm J, Bellin MD, Kibbey RG, Liesa M, Shirihai O. Mitochondrial Proton Leak Regulated by Cyclophilin D Elevates Insulin Secretion in Islets at Nonstimulatory Glucose Levels. Diabetes 2019, 69: 131-145. PMID: 31740442, PMCID: PMC6971491, DOI: 10.2337/db19-0379.Peer-Reviewed Original ResearchConceptsType 2 diabetesInsulin secretionInsulin resistanceFree fatty acidsNonesterified free fatty acidsGlucose-stimulated insulin secretionPrediabetic stateInsulin hypersecretionObese subjectsFatty acidsObese miceLean miceGlucose levelsHuman isletsPancreatic isletsΒ-cellsIsletsProton leakSecretionHyperinsulinemiaProgressive increaseDiabetesMiceMitochondrial proton leakLeak