2022
UCP2-dependent redox sensing in POMC neurons regulates feeding
Yoon N, Jin S, Kim J, Liu Z, Sun Q, Cardone R, Kibbey R, Diano S. UCP2-dependent redox sensing in POMC neurons regulates feeding. Cell Reports 2022, 41: 111894. PMID: 36577374, PMCID: PMC9885759, DOI: 10.1016/j.celrep.2022.111894.Peer-Reviewed Original ResearchConceptsPOMC neuronsGlucose metabolismPOMC neuronal activityAnorexigenic pro-opiomelanocortin (POMC) neuronsPro-opiomelanocortin (POMC) neuronsHigh-fat dietFatty acid metabolismMitochondrial respirationLactate levelsCerebrospinal fluidNeuronal activityGlucose utilizationFed stateNeuronsPyruvate levelsExtracellular pyruvate levelsAcid metabolismMalate-aspartate shuttleMetabolismAddition of lactateMitochondrial pyruvate carrierInhibitionObesityPyruvate carrierSatiety
2020
120-LB: Small Molecule Activator of Pyruvate Kinase Regulates In Vivo Glucose Homeostasis
ABULIZI A, CARDONE R, SIEBEL S, KUNG C, KIBBEY R. 120-LB: Small Molecule Activator of Pyruvate Kinase Regulates In Vivo Glucose Homeostasis. Diabetes 2020, 69 DOI: 10.2337/db20-120-lb.Peer-Reviewed Original ResearchEndogenous glucose productionNonalcoholic fatty liver diseaseWhole-body insulin sensitivityHFD-fed ratsInsulin sensitivityAgios PharmaceuticalsRegular chowInsulin resistanceBody weightInsulin-stimulated peripheral glucose uptakeGlucose productionHigh-fat diet ratsHyperinsulinemic-euglycemic clamp studiesSmall molecule activatorsMuscle triglyceride contentSevere liver dysfunctionFatty liver diseasePeripheral insulin sensitivityAmerican Diabetes AssociationWhole-body energy expenditurePeripheral glucose uptakeHigh-fat dietType 2 diabetesFat diet ratsPotential therapeutic target
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