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
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
Distinct Hepatic PKA and CDK Signaling Pathways Control Activity-Independent Pyruvate Kinase Phosphorylation and Hepatic Glucose Production
Gassaway BM, Cardone RL, Padyana AK, Petersen MC, Judd ET, Hayes S, Tong S, Barber KW, Apostolidi M, Abulizi A, Sheetz JB, Kshitiz, Aerni HR, Gross S, Kung C, Samuel VT, Shulman GI, Kibbey RG, Rinehart J. Distinct Hepatic PKA and CDK Signaling Pathways Control Activity-Independent Pyruvate Kinase Phosphorylation and Hepatic Glucose Production. Cell Reports 2019, 29: 3394-3404.e9. PMID: 31825824, PMCID: PMC6951436, DOI: 10.1016/j.celrep.2019.11.009.Peer-Reviewed Original ResearchConceptsCyclin-dependent kinasesMetabolic control pointPhosphorylation sitesNuclear retentionCDK activityPKL activityDays high-fat dietKinase phosphorylationImportant enzymePyruvate kinaseHigh-fat dietS113KinaseEnzyme kineticsPhosphorylationAdditional control pointsRegulationGlucose productionHepatic glucose productionInsulin resistanceGlycolysisEnzymePKAPathwayActivity