Inhibition of de novo ceramide synthesis by Sirtuin-1 improves beta-cell function and glucose metabolism in type 2 diabetes.
Srividya VelagapudiGergely KarsaiMaria KarsaiShafeeq A MohammedFabrizio MontecuccoLuca LiberaleHwan LeeFederico CarboneGiovanni Francesco AdamiKangmin YangMargot CrucetSokrates SteinFranceso PaneniTetiana Lapikova-BryhinskaHyun-Duk JangSimon KralerDaria VdovenkoRichard Arnold ZülligGiovanni G CamiciHyo-Soo KimReijo LaaksonenPhilipp A GerberThorsten HornemannAlexander AkhmedovThomas Felix LüscherPublished in: Cardiovascular research (2024)
Acetylation of TLR4 promotes β-cell dysfunction via ceramide synthesis in T2D, which is blunted by systemic SIRT1 replenishment. Hence, restoration of systemic SIRT1 may provide a novel therapeutic strategy to counteract toxic ceramide synthesis and mitigate cardiovascular complications of T2D.