Canagliflozin attenuates lipotoxicity in cardiomyocytes and protects diabetic mouse hearts by inhibiting the mTOR/HIF-1α pathway
Pengbo Sun, Yangyang Wang, Yipei Ding, Jingyi Luo, Jin Zhong, Naihan Xu, Yaou Zhang, Weidong Xie
Abstract
. The results showed that CAN significantly ameliorated heart functions and inflammatory responses in the hearts of the HFD/STZ-induced diabetic mice. CAN significantly attenuated the inflammatory injury induced by PA in the HL-1 cells. Furthermore, CAN seemed to bind to the mammalian target of rapamycin (mTOR) and then inhibit mTOR phosphorylation and hypoxia-inducible factor-1α (HIF-1α) expression. These results indicated that CAN might attenuate lipotoxicity in cardiomyocytes by inhibiting the mTOR/HIF-1α pathway and then show protective effects on diabetic hearts.
Topics & Concepts
LipotoxicityPI3K/AKT/mTOR pathwayCanagliflozinChemistryStreptozotocinInternal medicineEndocrinologyDiabetic cardiomyopathyIn vivoApoptosisDiabetic nephropathyPharmacologyDiabetes mellitusMedicineHeart failureType 2 diabetesBiologyInsulin resistanceBiochemistryCardiomyopathyBiotechnologyDiabetes Treatment and ManagementPancreatic function and diabetesMetabolism, Diabetes, and Cancer