Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016:2016:4219735.
doi: 10.1155/2016/4219735. Epub 2015 Nov 30.

Exenatide Activates the APPL1-AMPK-PPARα Axis to Prevent Diabetic Cardiomyocyte Apoptosis

Lei XiaoTian  1 , Wu QiNan  1 , Gan XiaGuang  1 , Deng WuQuan  1 , Chen Bing  1 , Liang ZiWen  1
Affiliations

Exenatide Activates the APPL1-AMPK-PPARα Axis to Prevent Diabetic Cardiomyocyte Apoptosis

Lei XiaoTian et al. J Diabetes Res. 2016.

Abstract

Objective: To investigate the effect and mechanism of the exenatide on diabetic cardiomyopathy.

Methods: Rats were divided into control group, diabetes group (D), diabetes treated with insulin (DI) group, and diabetes treat with exenatide (DE) group. We detected apoptosis rate by TUNEL, the adiponectin and high molecular weight adiponectin (HMW-adiponectin) by ELISA, and the expression of APPL1, p-AMPK/T-AMPK, PPARα, and NF-κB by immunohistochemistry and western blotting.

Results: Compared with the D group, the apoptosis in the Control and DE groups was decreased (P < 0.05); the adiponectin and HMW-adiponectin were increased (P < 0.05); the APPL1, p-AMPK/T-AMPK, PPARα, and LV -dP/dt were increased (P < 0.05); and the NF-κB, GRP78, and LVEDP were decreased (P < 0.05). Compared with DE group, the glucose levels in the DI group were similar (P < 0.05); the apoptosis and LVEDP were increased; the APPL1, p-AMPK/T-AMPK, PPARα, and LV -dP/dt were decreased (P < 0.05); the NF-κB and GRP78 were increased (P < 0.05); the adiponectin and HMW-adiponectin were significantly decreased (P < 0.05).

Conclusion: Our model of diabetic cardiomyopathy was constructed successfully. After being treated with exenatide, the adiponectin and HMW-adiponectin and the APPL1-AMPK-PPARα axis were increased, the NF-κB and the apoptosis were decreased, the cardiac function of the diabetic rats was improved, and these effects were independent of glucose control.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The cardiac function of each group. ∗ compared with the D group, P < 0.05; # compared with the DI group, P < 0.05.
Figure 2
Figure 2
Myocardial apoptosis in each group ×400.
Figure 3
Figure 3
The apoptosis rate in each group. ∗ compared with the D group, P < 0.05; # compared with the DI group, P < 0.05.
Figure 4
Figure 4
APPL1 expression in each group ×200.
Figure 5
Figure 5
p-AMPK expression in each group ×200.
Figure 6
Figure 6
PPARα expression in each group ×200.
Figure 7
Figure 7
NF-κB expression in each group ×200.
Figure 8
Figure 8
Protein expression levels of APPL1, p-AMPK/T-AMPK, PPARα, GRP78, and NF-κB in each group.
Figure 9
Figure 9
The protein expression levels of APPL1, p-AMPK/T-AMPK, PPARα, NF-κB, and GRP78 in each group. ∗ compared with the D group, P < 0.05; # compared with the DI group, P < 0.05.
See this image and copyright information in PMC

References

    1. Battiprolu P. K., Hojayev B., Jiang N., et al. Metabolic stress-induced activation of FoxO1 triggers diabetic cardiomyopathy in mice. The Journal of Clinical Investigation. 2012;122(3):1109–1118. doi: 10.1172/jci60329. - DOI - PMC - PubMed
    1. Despa S., Margulies K. B., Chen L., et al. Hyperamylinemia contributes to cardiac dysfunction in obesity and diabetes: a study in humans and rats. Circulation Research. 2012;110(4):598–608. doi: 10.1161/circresaha.111.258285. - DOI - PMC - PubMed
    1. Rubin J., Matsushita K., Ballantyne C. M., Hoogeveen R., Coresh J., Selvin E. Chronic hyperglycemia and subclinical myocardial injury. Journal of the American College of Cardiology. 2012;59(5):484–489. doi: 10.1016/j.jacc.2011.10.875. - DOI - PMC - PubMed
    1. Jaleel F., Jaleel A., Aftab J., Rahman M. A. Relationship between adiponectin, glycemic control and blood lipids in diabetic type 2 postmenopausal women with and without complication of ischemic heart disease. Clinica Chimica Acta. 2006;370(1-2):76–81. doi: 10.1016/j.cca.2006.01.022. - DOI - PubMed
    1. Bråkenhielm E., Veitonmäki N., Cao R., et al. Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proceedings of the National Academy of Sciences of the United States of America. 2004;101(8):2476–2481. doi: 10.1073/pnas.0308671100. - DOI - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources