β-cell deletion of the PKm1 and PKm2 isoforms of pyruvate kinase in mice reveals their essential role as nutrient sensors for the KATP channel
Foster HR, Ho T, Potapenko E, Sdao SM, Huang SM, Lewandowski SL, VanDeusen HR, Davidson SM, Cardone RL, Prentki M, Kibbey RG, Merrins MJ. β-cell deletion of the PKm1 and PKm2 isoforms of pyruvate kinase in mice reveals their essential role as nutrient sensors for the KATP channel. ELife 2022, 11: e79422. PMID: 35997256, PMCID: PMC9444242, DOI: 10.7554/elife.79422.Peer-Reviewed Original ResearchConceptsPyruvate kinaseATP/ADPCytosolic ATP/ADPAmino acidsPKM2 isoformPK isoformsPlasma membraneNutrient sensorNutrient responsesPEP carboxykinasePKM1Mitochondrial sourcesPKM2Channel closureEssential roleInsulin secretionDifferential responsePK activityKinaseMembrane depolarizationIsoformsDeletionATPKey roleADPβ Cell–specific deletion of Zfp148 improves nutrient-stimulated β cell Ca2+ responses
Emfinger CH, de Klerk E, Schueler KL, Rabaglia ME, Stapleton DS, Simonett SP, Mitok KA, Wang Z, Liu X, Paulo JA, Yu Q, Cardone RL, Foster HR, Lewandowski SL, Perales JC, Kendziorski CM, Gygi SP, Kibbey RG, Keller MP, Hebrok M, Merrins MJ, Attie AD. β Cell–specific deletion of Zfp148 improves nutrient-stimulated β cell Ca2+ responses. JCI Insight 2022, 7: e154198. PMID: 35603790, PMCID: PMC9220824, DOI: 10.1172/jci.insight.154198.Peer-Reviewed Original ResearchConceptsCell-specific deletionΒ-cell Ca2Insulin secretionAmino acid metabolismLow glucose conditionsRNA-seqPancreatic β-cellsLevels of enzymesZfp148Glutamate dehydrogenaseIntermediary metabolismChannel closureEnhanced insulin secretionWestern-style dietControl mice fedElevated glucose levelsAcid metabolismΒ-cellsCell functionGlucose toleranceCell Ca2Elevated sensitivityGlucose conditionsMetabolic challengesMice fed