Exenatide reduces cardiomyocyte apoptosis by stimulating adiponectin secretion and activating APPL1-AMPK-PPARα axis

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, PPAR alpha and NF-kappa B 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 PPAR alpha was down-regulated and that of NF-kappa B 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 PPAR alpha was up-regulated and that of NF-kappa B 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 PPAR alpha was up-regulated and that of NF-kappa B 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 PPAR alpha was down-regulated and that of NF-kappa B was up-regulated compared with group DE (P<0.05). Conclusions: Exenatide can activate the APPL1-AMPK-PPAR alpha anti-apoptosis signaling axis by promoting adiponectin expression in cardiomyocytes and reducing the apoptosis of diabetic cardiomyocytes, thus protecting cardiomyocytes.