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
Pyruvate Kinase Controls Signal Strength in the Insulin Secretory Pathway
Lewandowski SL, Cardone RL, Foster HR, Ho T, Potapenko E, Poudel C, VanDeusen HR, Sdao SM, Alves TC, Zhao X, Capozzi ME, de Souza AH, Jahan I, Thomas CJ, Nunemaker CS, Davis DB, Campbell JE, Kibbey RG, Merrins MJ. Pyruvate Kinase Controls Signal Strength in the Insulin Secretory Pathway. Cell Metabolism 2020, 32: 736-750.e5. PMID: 33147484, PMCID: PMC7685238, DOI: 10.1016/j.cmet.2020.10.007.Peer-Reviewed Original ResearchConceptsPyruvate kinaseATP/ADPΒ-cell metabolismAppropriate insulin secretionPotential therapeutic routeSecretory pathwayMitochondrial fuelsPancreatic β-cellsInsulin secretory pathwayOxidative phosphorylationCell metabolismNutrient metabolismPhosphoenolpyruvateCell sensingPK activatorΒ-cellsCell functionInsulin secretionPK activityOxidative functionMembrane depolarizationMitochondriaPK activationΒ-cell functionADPMulti-Tissue Acceleration of the Mitochondrial Phosphoenolpyruvate Cycle Improves Whole-Body Metabolic Health
Abulizi A, Cardone RL, Stark R, Lewandowski SL, Zhao X, Hillion J, Ma L, Sehgal R, Alves TC, Thomas C, Kung C, Wang B, Siebel S, Andrews ZB, Mason GF, Rinehart J, Merrins MJ, Kibbey RG. Multi-Tissue Acceleration of the Mitochondrial Phosphoenolpyruvate Cycle Improves Whole-Body Metabolic Health. Cell Metabolism 2020, 32: 751-766.e11. PMID: 33147485, PMCID: PMC7679013, DOI: 10.1016/j.cmet.2020.10.006.Peer-Reviewed Original ResearchConceptsInsulin secretionInsulin sensitivityPK activatorWhole-body metabolic healthPK activationMetabolic homeostasisPeripheral insulin sensitivityHFD-fed ratsEndogenous glucose productionPreclinical rodent modelsHigher insulin contentPreclinical rationaleLiver fatMetabolic healthMarkers of differentiationIslet functionRodent modelsGlucose homeostasisInsulin contentPancreatic isletsGlucose productionGlucose turnoverMitochondrial PEPCKSecretionHomeostasis