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

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 upregulated 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.

Ononin alleviates H2O2‑induced cardiomyocyte apoptosis and improves cardiac function by activating the AMPK/mTOR/autophagy pathway

“…However, only p-AMPK levels were firmly enhanced after ON treatment. The benefits of p-AMPK stimulation have been previously observed in many cardiovascular diseases, including MI and ischemia reperfusion injury (36)(37)(38). In the present study, AMPK activation inhibited the phosphorylation of mTOR, leading to an increase in autophagy.…”

Effect of Metformin on Breast Density in Overweight/Obese Premenopausal Women

“…On the one hand, the breast density in premenopausal women is higher than that in postmenopausal women; therefore, the improvement in the difference may be more obvious. On the other hand, previous studies suggested that diabetic patients have lower levels of adiponectin than healthy people and that improvement in lifestyle can also improve the adiponectin levels, 51 which may contribute to reducing breast density.…”

GLP1 Receptor Agonists—Effects beyond Obesity and Diabetes

“…In a study of diabetic rats, the GLP1RA exenatide decreased cardiomyocyte apoptosis and improved cardiac function. This effect was associated with increased AMPK phosphorylation, activating its activity [ 106 ]. In addition, it has been reported that liraglutide ameliorates the lipotoxic, inflammatory effects of high-calorie diet feeding in vivo and palmitic acid treatment in vitro via inhibition of the mTORC1 signaling pathway [ 107 ].…”