2023
Loss of ZNF148 enhances insulin secretion in human pancreatic β cells
de Klerk E, Xiao Y, Emfinger C, Keller M, Berrios D, Loconte V, Ekman A, White K, Cardone R, Kibbey R, Attie A, Hebrok M. Loss of ZNF148 enhances insulin secretion in human pancreatic β cells. JCI Insight 2023, 8: e157572. PMID: 37288664, PMCID: PMC10393241, DOI: 10.1172/jci.insight.157572.Peer-Reviewed Original ResearchConceptsPancreatic β-cellsΒ-cellsSC-β cellsHuman pancreatic β-cellsInsulin secretionHuman β-cellsVesicle traffickingGenetic regulatorsStem cell-derived β cellsDirect repressionS100 genesCells identifiesZNF148Annexin A2Tetrameric complexCell membraneNovel therapeutic targetNovel therapeutic strategiesHuman isletsRegulatorTherapeutic targetCellsS100A16 expressionGlucose homeostasisTherapeutic strategies
2022
β 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
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