Xiaotian Lei1, Qinan Wu2, Weiling Leng1, Minxia Wu3, Liu Chen1, Ziwen Liang1. 1. Department of Endocrinology, Southwest Hospital, the Third Military Medical University (Army Medical University), Chongqing 400038, China. 2. Department of Endocrine Nephropathy, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing 400038, China. 3. Health Management Center, Southwest Hospital, the Third Military Medical University (Army Medical University), Chongqing 400038, China.
Abstract
BACKGROUND: To explore the mechanism that exenatide reduces cardiomyocyte apoptosis via the adiponectin pathway in vitro. METHODS: Cardiomyocytes were randomly divided into the control group (group C), diabetic group (group D), diabetic + exenatide treatment group (group DE), diabetic + exenatide treatment + APPL1 overexpression group (group OE), and diabetic + exenatide treatment + APPL1 knock-down group (group KD). After 48 h culture, the apoptosis rate, the adiponectin level in the cell culture fluid, and the expression levels of APPL1, p-AMPK, PPARα and NF-κB were detected by TUNEL, ELISA, and Western blotting, respectively. RESULTS: Compared to group C, the apoptosis rate was markedly increased, the adiponectin level was decreased, the expression of APPL1, p-AMPK and PPARα was down-regulated and that of NF-κB was up-regulated in group D (P<0.05); in group DE, the apoptosis rate was significantly decreased, the expression of APPL1, p-AMPK and PPARα was up-regulated and that of NF-κB was down-regulated, as compared with group D (P<0.05). The apoptosis rate in group OE was lower than that in group DE, the expression of APPL1, p-AMPK and PPARα was up-regulated and that of NF-κB was down-regulated (P<0.05). In group KD, the adiponectin level was elevated and the cardiomyocyte apoptosis rate was increased, as compared to group D (P<0.05). Furthermore, the expression of APPL1, p-AMPK and PPARα was down-regulated and that of NF-κB was up-regulated compared with group DE (P<0.05). CONCLUSIONS: Exenatide can activate the "APPL1-AMPK-PPARα" anti-apoptosis signaling axis by promoting adiponectin expression in cardiomyocytes and reducing the apoptosis of diabetic cardiomyocytes, thus protecting cardiomyocytes.
BACKGROUND: To explore the mechanism that exenatide reduces cardiomyocyte apoptosis via the adiponectin pathway in vitro. METHODS: Cardiomyocytes were randomly divided into the control group (group C), diabetic group (group D), diabetic + exenatide treatment group (group DE), diabetic + exenatide treatment + APPL1 overexpression group (group OE), and diabetic + exenatide treatment + APPL1 knock-down group (group KD). After 48 h culture, the apoptosis rate, the adiponectin level in the cell culture fluid, and the expression levels of APPL1, p-AMPK, PPARα and NF-κB were detected by TUNEL, ELISA, and Western blotting, respectively. RESULTS: Compared to group C, the apoptosis rate was markedly increased, the adiponectin level was decreased, the expression of APPL1, p-AMPK and PPARα was down-regulated and that of NF-κB was up-regulated in group D (P<0.05); in group DE, the apoptosis rate was significantly decreased, the expression of APPL1, p-AMPK and PPARα was up-regulated and that of NF-κB was down-regulated, as compared with group D (P<0.05). The apoptosis rate in group OE was lower than that in group DE, the expression of APPL1, p-AMPK and PPARα was up-regulated and that of NF-κB was down-regulated (P<0.05). In group KD, the adiponectin level was elevated and the cardiomyocyte apoptosis rate was increased, as compared to group D (P<0.05). Furthermore, the expression of APPL1, p-AMPK and PPARα was down-regulated and that of NF-κB was up-regulated compared with group DE (P<0.05). CONCLUSIONS: Exenatide can activate the "APPL1-AMPK-PPARα" anti-apoptosis signaling axis by promoting adiponectin expression in cardiomyocytes and reducing the apoptosis of diabetic cardiomyocytes, thus protecting cardiomyocytes.
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