Small molecules targeting selective PCK1 and PGC-1α lysine acetylation cause anti-diabetic action through increased lactate oxidation
Mutlu B, Sharabi K, Sohn J, Yuan B, Latorre-Muro P, Qin X, Yook J, Lin H, Yu D, Camporez J, Kajimura S, Shulman G, Hui S, Kamenecka T, Griffin P, Puigserver P. Small molecules targeting selective PCK1 and PGC-1α lysine acetylation cause anti-diabetic action through increased lactate oxidation. Cell Chemical Biology 2024, 31: 1772-1786.e5. PMID: 39341205, PMCID: PMC11500315, DOI: 10.1016/j.chembiol.2024.09.001.Peer-Reviewed Original ResearchPhosphoenolpyruvate carboxykinase 1Lysine acetylationTricarboxylic acidAnti-diabetic effectsAnaplerotic reactionsGluconeogenic reactionsLiver-specific expressionGluconeogenic metabolitesLactate oxidationSmall moleculesAnti-diabetic actionSuppressed gluconeogenesisHepatic glucose productionPGC-1aAcetylationOxaloacetateGluconeogenesisObese miceGlucose productionIncreased glucoseGlucose oxidationSubstrate oxidationOxidationGlucoseMutants