2022
Metabolic cycles and signals for insulin secretion
Merrins MJ, Corkey BE, Kibbey RG, Prentki M. Metabolic cycles and signals for insulin secretion. Cell Metabolism 2022, 34: 947-968. PMID: 35728586, PMCID: PMC9262871, DOI: 10.1016/j.cmet.2022.06.003.Peer-Reviewed Original Research316-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
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 functionADP