2022
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 roleADP316-OR: Genetic Deletion of Beta-Cell Pkm1, Pkm2, and Pck2 Identifies PEP as an Essential Signal for Compartmentalized KATP Closure and Cycling of the Insulin Secretory Pathway
FOSTER H, HO T, POTAPENKO E, CARDONE R, KIBBEY R, MERRINS M. 316-OR: Genetic Deletion of Beta-Cell Pkm1, Pkm2, and Pck2 Identifies PEP as an Essential Signal for Compartmentalized KATP Closure and Cycling of the Insulin Secretory Pathway. Diabetes 2022, 71 DOI: 10.2337/db22-316-or.Peer-Reviewed Original ResearchΒ-cell-specific deletionΒ-cell metabolismStrong genetic evidenceSense nutrientsNutrient-stimulated insulin secretionAppropriate insulin secretionSecretory pathwayPKM2 isoformGenetic evidenceInsulin secretory pathwayPKM isoformsPKM1PCK2Essential signalAmino acidsPKM2Pyruvate kinaseADP generationΒ-cell responseInitiation of Ca2Genetic deletionIsoform expressionΒ-cellsDeletionInsulin secretion
2018
Cyclophilin D-Dependent Mitochondrial Proton Leak in ß Cells Promotes Basal Insulin Secretion
ALSABEEH N, TADDEO E, WIKSTRÖM J, RITOU E, STILES L, KIBBEY R, LIESA M, SHIRIHAI O. Cyclophilin D-Dependent Mitochondrial Proton Leak in ß Cells Promotes Basal Insulin Secretion. Diabetes 2018, 67 DOI: 10.2337/db18-312-lb.Peer-Reviewed Original ResearchMitochondrial proton leakProton leakPermeability transition poreInhibition of CypDBasal hypersecretionCyclophilin DMolecular mechanismsInsulin secretionTransition poreGenetic inhibitionHigh-fat diet animalsAmino acidsDevelopment of diabetesHypersecretion of insulinNovel targetBeta-cell failureBasal insulin secretionBasal hyperinsulinemiaFatty acidsPrediabetic subjectsPrediabetic animalsLow conductance stateBlood glucoseBasal secretionPharmacological stimulation