Mingming Zhang1, Shanjie Wang1, Zheng Cheng1, Zhenyu Xiong1, Jianjun Lv2, Zhi Yang2, Tian Li2, Shuai Jiang2, Jing Gu3, Dongdong Sun4, Yanhong Fan5. 1. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China; Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China. 2. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. 3. School of Basic Medical Sciences, Fourth Military Medical University, China. 4. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: wintersun3@gmail.com. 5. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: FanYH1@fmmu.edu.cn.
Abstract
BACKGROUND: Diabetic cardiomyopathy is identified as cardiac ventricular dysfunction induced by an insulin shortage in diabetic patients. Our previous studies have shown that Polydatin (PD) alleviates cardiac dysfunction after myocardial infarction (MI) injury. Nevertheless, the mechanism by which PD regulates diabetic cardiomyopathy has not been reported. METHODS: In this study, we demonstrated the effects and described the mechanisms of PD in diabetic cardiomyopathy in both adult mouse hearts and neonatal mouse cardiomyocytes. We injected streptozotocin (STZ) to induce the DM model in wild-type (WT) and Sirt3 knockout (Sirt3-/-) mice. Mitochondrial bioenergetics in diabetic mice were detected by measuring citrate synthase activity and ATP content. The extent of autophagy regulation by PD was investigated by detecting the levels of Beclin 1, Atg5, LC3 and p62. RESULTS: Compared to the WT mouse hearts, hearts from the diabetic mice exhibited better cardiac function and a higher level of autophagy. Moreover, mitochondrial function in the diabetic mouse hearts was improved after PD treatment. However, PD treatment had no effect on the Sirt3 knockout diabetic mouse hearts. Additionally, PD increased autophagy flux in the cardiomyocytes that were cultured in high-glucose medium for 48 h. In addition, PD had no effects on the cardiomyocytes under high-glucose conditions when we down-regulated Sirt3. CONCLUSIONS: Altogether, PD attenuated cardiac dysfunction, increased autophagy flux and improved mitochondrial bioenergetics by up-regulating Sirt3 in the diabetic mice.
BACKGROUND:Diabetic cardiomyopathy is identified as cardiac ventricular dysfunction induced by an insulin shortage in diabeticpatients. Our previous studies have shown that Polydatin (PD) alleviates cardiac dysfunction after myocardial infarction (MI) injury. Nevertheless, the mechanism by which PD regulates diabetic cardiomyopathy has not been reported. METHODS: In this study, we demonstrated the effects and described the mechanisms of PD in diabetic cardiomyopathy in both adult mouse hearts and neonatal mouse cardiomyocytes. We injected streptozotocin (STZ) to induce the DM model in wild-type (WT) and Sirt3 knockout (Sirt3-/-) mice. Mitochondrial bioenergetics in diabeticmice were detected by measuring citrate synthase activity and ATP content. The extent of autophagy regulation by PD was investigated by detecting the levels of Beclin 1, Atg5, LC3 and p62. RESULTS: Compared to the WT mouse hearts, hearts from the diabeticmice exhibited better cardiac function and a higher level of autophagy. Moreover, mitochondrial function in the diabeticmouse hearts was improved after PD treatment. However, PD treatment had no effect on the Sirt3 knockout diabeticmouse hearts. Additionally, PD increased autophagy flux in the cardiomyocytes that were cultured in high-glucose medium for 48 h. In addition, PD had no effects on the cardiomyocytes under high-glucose conditions when we down-regulated Sirt3. CONCLUSIONS: Altogether, PD attenuated cardiac dysfunction, increased autophagy flux and improved mitochondrial bioenergetics by up-regulating Sirt3 in the diabeticmice.