TY - JOUR AB - Decreasing phosphorylation of AKT‑Foxo1 is closely associated with the onset of insulin resistance and apoptosis during diabetic cardiomyopathy (DCM). Opening of mitochondrial ATP‑sensitive potassium channels (mitoKATP) increases the expression of p‑AKT in the process of reperfusion injury. It was therefore hypothesized that opening of mitoKATP may regulate the AKT‑Foxo1 signaling pathway and improve cardiac function in DCM. In the present study, opening of mitoKATP by diazoxide (DZX) was found to improve cardiac function and attenuate cardiomyocyte apoptosis in db/db mice. DZX also significantly increased the expression of p‑AKT and p‑Foxo1. Similarly, DZX decreased the expression of the heart failure marker NT‑proBNP, increased mitochondrial membrane potential, inhibited apoptosis, and increased the expression of p‑AKT and p‑Foxo1 when mimicking insulin resistance in cultured cardiomyocytes. Moreover, the protective effects of DZX were completely blocked by the specific AKT inhibitor MK‑2206. These data suggest that the regulation of the AKT‑Foxo1 signaling pathway by mitoKATP plays an important role in improving cardiac function and inhibiting apoptosis in DCM, and may therefore be a new potential therapeutic target for DCM. AD - Department of Cardiology, Chinese PLA General Hospital, Beijing 100853, P.R. China Department of Cardiology, Chinese PLA No. 371 Hospital, Xinxiang, Henan 453000, P.R. China Department of Medical Administration, Chinese PLA No. 371 Hospital, Xinxiang, Henan 453000, P.R. China AU - Duan,Peng AU - Wang,Jinxin AU - Li,Yang AU - Wei,Shiqiang AU - Su,Feng AU - Zhang,Sanlin AU - Duan,Yuhui AU - Wang,Lin AU - Zhu,Qinglei DA - 2018/11/01 DO - 10.3892/ijmm.2018.3832 EP - 2719 IS - 5 JO - Int J Mol Med KW - diabetic cardiomyopathy mitochondrial membrane potential insulin resistance diazoxide PY - 2018 SN - 1107-3756 1791-244X SP - 2709 ST - Opening of mitoKATP improves cardiac function and inhibits apoptosis via the AKT-Foxo1 signaling pathway in diabetic cardiomyopathy T2 - International Journal of Molecular Medicine TI - Opening of mitoKATP improves cardiac function and inhibits apoptosis via the AKT-Foxo1 signaling pathway in diabetic cardiomyopathy UR - https://doi.org/10.3892/ijmm.2018.3832 VL - 42 ER -