2021
127-OR: In Vivo Genetic Evidence That the Pyruvate Kinase Isoforms PKM1 and PKM2 Differentially Control Beta-Cell Fuel Sensing
FOSTER H, HO T, POTAPENKO E, LEWANDOWSKI S, SDAO S, VANDEUSEN H, CARDONE R, KIBBEY R, MERRINS M. 127-OR: In Vivo Genetic Evidence That the Pyruvate Kinase Isoforms PKM1 and PKM2 Differentially Control Beta-Cell Fuel Sensing. Diabetes 2021, 70 DOI: 10.2337/db21-127-or.Peer-Reviewed Original ResearchInsulin secretionPK activatorΒ-cellsNational InstituteIntact β-cellsAppropriate insulin secretionGlucose intoleranceΒ-cell-specific deletionCalcium influxVivo genetic evidenceCalcium defectsHealth resourcesLow glucoseElectrophysiological evidenceIsletsMembrane depolarizationMiceServices AdministrationSecretionExcised membrane patchesSpecific deletionMitochondrial fuelsCalcium oscillationsPKM2KATP
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