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Article

Exendin-4, a glucagon‑like peptide‑1 receptor agonist, inhibits hyperglycemia‑induced apoptosis in myocytes by suppressing receptor for advanced glycation end products expression

  • Authors:
    • Bo Yi
    • Xiaorong Hu
    • Zhongyuan Wen
    • Ting Zhang
    • Yuli Cai
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
  • Pages: 1185-1190
    |
    Published online on: July 31, 2014
       https://doi.org/10.3892/etm.2014.1873
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Abstract

Activation of the receptor for advanced glycation end products (RAGE) axis may have an important role in apoptosis. Glucagon‑like peptide‑1 (GLP‑1) is a gut hormone that has been proposed as a therapeutic target for the treatment of diabetes, and GLP‑1 receptor agonists have been reported to protect against myocardial injury associated with diabetes. The aim of the present study was to investigate the cardioprotective mechanism of exendin‑4 (EX‑4), a GLP‑1 receptor agonist, against myocardial cell apoptosis induced by hyperglycemia. Neonatal rat ventricular myocytes were prepared by enzymatic dissociation and then cultured with high levels of glucose (HG) in the presence or absence of EX‑4. Cell apoptosis was detected using an annexin V‑fluorescein isothiocyanate/propidium iodide kit, and cell viability was measured using an MTT assay. RAGE expression levels and the activity of caspase‑3 were assessed by western blot analysis. The results demonstrated that the incubation of myocytes with HG led to a time‑dependent activation of RAGE, and the protein expression of RAGE was increased at 6 h and peaked at 24 h (P<0.05). Hyperglycemia was also found to significantly decrease cell viability and increase apoptosis (P<0.05). In addition, EX‑4 significantly inhibited hyperglycemia‑induced RAGE expression and the apoptosis of myocytes, and improved cell viability in a dose‑dependent manner (P<0.05). When the concentration of EX‑4 was 10 nM, the myocardial cell viability was significantly improved, and the levels of RAGE expression and apoptosis were significantly decreased compared with those in the HG group in the absence of EX‑4 (P<0.05). Therefore, the results from the present study suggest that the cardioprotective effect induced by EX‑4, a GLP‑1 receptor agonist, against diabetic cardiomyopathy may be associated with the inhibition of RAGE expression.
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1 

Cai L, Li W, Wang G, Guo L, Jiang Y and Kang YJ: Hyperglycemia-induced apoptosis in mouse myocardium: mitochondrial cytochrome c-mediated caspase-3 activation pathway. Diabetes. 51:1938–1948. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Li Z, Zhang T, Dai H, et al: Involvement of endoplasmic reticulum stress in myocardial apoptosis of streptozocin-induced diabetic rats. J Clin Biochem Nutr. 41:58–67. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Kuethe F, Sigusch HH, Bornstein SR, Hilbig K, Kamvissi V and Figulla HR: Apoptosis in patients with dilated cardiomyopathy and diabetes: a feature of diabetic cardiomyopathy? Horm Metab Res. 39:672–676. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Yu XY, Song YH, Geng YJ, et al: Glucose induces apoptosis of cardiomyocytes via microRNA-1 and IGF-1. Biochem Biophys Res Commun. 376:548–552. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Liang JL, Xiao DZ, Liu XY, et al: High glucose induces apoptosis in AC16 human cardiomyocytes via macrophage migration inhibitory factor and c-Jun N-terminal kinase. Clin Exp Pharmacol Physiol. 37:969–973. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Fiordaliso F, Bianchi R, Staszewsky L, et al: Antioxidant treatment attenuates hyperglycemia-induced cardiomyocyte death in rats. J Mol Cell Cardiol. 37:959–968. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Neeper M, Schmidt AM, Brett J, et al: Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem. 267:14998–15004. 1992.PubMed/NCBI

8 

Yan SF, Ramasamy R and Schmidt AM: Receptor for AGE (RAGE) and its ligands - cast into leading roles in diabetes and the inflammatory response. J Mol Med (Berl). 87:235–247. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Yao D and Brownlee M: Hyperglycemia-induced reactive oxygen species increase expression of the receptor for advanced glycation end products (RAGE) and RAGE ligands. Diabetes. 59:249–255. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Zong H, Ward M, Madden A, et al: Hyperglycaemia-induced pro-inflammatory responses by retinal Müller glia are regulated by the receptor for advanced glycation end-products (RAGE). Diabetologia. 53:2656–2666. 2010.PubMed/NCBI

11 

Bucciarelli LG, Ananthakrishnan R, Hwang YC, et al: RAGE and modulation of ischemic injury in the diabetic myocardium. Diabetes. 57:1941–1951. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Mannucci E and Rotella CM: Future perspectives on glucagon-like peptide-1, diabetes and cardiovascular risk. Nutr Metab Cardiovasc Dis. 18:639–645. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Hiki M, Shimada K, Kiyanagi T, et al: Single administration of alpha-glucosidase inhibitors on endothelial function and incretin secretion in diabetic patients with coronary artery disease - Juntendo University trial: effects of miglitol on endothelial vascular reactivity in type 2 diabetic patients with coronary heart disease (J-MACH). Circ J. 74:1471–1478. 2010.

14 

Nikolaidis LA, Mankad S, Sokos GG, et al: Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation. 109:962–965. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Sokos GG, Nikolaidis LA, Mankad S, Elahi D and Shannon RP: Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure. J Card Fail. 12:694–699. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Halbirk M, Nørrelund H, Møller N, et al: Cardiovascular and metabolic effects of 48-h glucagon-like peptide-1 infusion in compensated chronic patients with heart failure. Am J Physiol Heart Circ Physiol. 298:H1096–H1102. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Brown SB, Libonati JR, Selak MA, Shannon RP and Simmons RA: Neonatal exendin-4 leads to protection from reperfusion injury and reduced rates of oxidative phosphorylation in the adult rat heart. Cardiovasc Drugs Ther. 24:197–205. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Sonne DP, Engstrøm T and Treiman M: Protective effects of GLP-1 analogues exendin-4 and GLP-1(9–36) amide against ischemia-reperfusion injury in rat heart. Regul Pept. 146:243–249. 2008.PubMed/NCBI

19 

Barakat GM, Nuwayri-Salti N, Kadi LN, Bitar KM, Al-Jaroudi WA and Bikhazi AB: Role of glucagon-like peptide-1 and its agonists on early prevention of cardiac remodeling in type 1 diabetic rat hearts. Gen Physiol Biophys. 30:34–44. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Hu X, Zhou X, He B, et al: Minocycline protects against myocardial ischemia and reperfusion injury by inhibiting high mobility group box 1 protein in rats. Eur J Pharmacol. 638:84–89. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Anderson EJ, Rodriguez E, Anderson CA, Thayne K, Chitwood WR and Kypson AP: Increased propensity for cell death in diabetic human heart is mediated by mitochondrial-dependent pathways. Am J Physiol Heart Circ Physiol. 300:H118–H124. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Kim SW, Lim CM, Kim JB, et al: Extracellular HMGB1 released by NMDA treatment confers neuronal apoptosis via RAGE-p38 MAPK/ERK signaling pathway. Neurotox Res. 20:159–169. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Zhu Y, Shu T, Lin Y, et al: Inhibition of the receptor for advanced glycation endproducts (RAGE) protects pancreatic β-cells. Biochem Biophys Res Commun. 404:159–165. 2011.PubMed/NCBI

24 

Jin Q, Chen H, Luo A, Ding F and Liu Z: S100A14 stimulates cell proliferation and induces cell apoptosis at different concentrations via receptor for advanced glycation end products (RAGE). PLoS One. 6:e193752011. View Article : Google Scholar : PubMed/NCBI

25 

Davidson MH: Cardiovascular effects of glucagonlike peptide-1 agonists. Am J Cardiol. 108:33B–41B. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Ravassa S, Zudaire A, Carr RD and Díez J: Antiapoptotic effects of GLP-1 in murine HL-1 cardiomyocytes. Am J Physiol Heart Circ Physiol. 300:H1361–H1372. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Chen TH, Wo HT, Wu CC, et al: Exendin-4 attenuates lipopolysaccharides induced inflammatory response but does not protects H9c2 cells from apoptosis. Immunopharmacol Immunotoxicol. 34:484–490. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Ishibashi Y, Nishino Y, Matsui T, Takeuchi M and Yamagishi S: Glucagon-like peptide-1 suppresses advanced glycation end product-induced monocyte chemoattractant protein-1 expression in mesangial cells by reducing advanced glycation end product receptor level. Metabolism. 60:1271–1277. 2011. View Article : Google Scholar

29 

Ishibashi Y, Matsui T, Takeuchi M and Yamagishi S: Glucagon-like peptide-1 (GLP-1) inhibits advanced glycation end product (AGE)-induced up-regulation of VCAM-1 mRNA levels in endothelial cells by suppressing AGE receptor (RAGE) expression. Biochem Biophys Res Commun. 391:1405–1408. 2010. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yi B, Hu X, Wen Z, Zhang T and Cai Y: Exendin-4, a glucagon‑like peptide‑1 receptor agonist, inhibits hyperglycemia‑induced apoptosis in myocytes by suppressing receptor for advanced glycation end products expression. Exp Ther Med 8: 1185-1190, 2014.
APA
Yi, B., Hu, X., Wen, Z., Zhang, T., & Cai, Y. (2014). Exendin-4, a glucagon‑like peptide‑1 receptor agonist, inhibits hyperglycemia‑induced apoptosis in myocytes by suppressing receptor for advanced glycation end products expression. Experimental and Therapeutic Medicine, 8, 1185-1190. https://doi.org/10.3892/etm.2014.1873
MLA
Yi, B., Hu, X., Wen, Z., Zhang, T., Cai, Y."Exendin-4, a glucagon‑like peptide‑1 receptor agonist, inhibits hyperglycemia‑induced apoptosis in myocytes by suppressing receptor for advanced glycation end products expression". Experimental and Therapeutic Medicine 8.4 (2014): 1185-1190.
Chicago
Yi, B., Hu, X., Wen, Z., Zhang, T., Cai, Y."Exendin-4, a glucagon‑like peptide‑1 receptor agonist, inhibits hyperglycemia‑induced apoptosis in myocytes by suppressing receptor for advanced glycation end products expression". Experimental and Therapeutic Medicine 8, no. 4 (2014): 1185-1190. https://doi.org/10.3892/etm.2014.1873
Copy and paste a formatted citation
x
Spandidos Publications style
Yi B, Hu X, Wen Z, Zhang T and Cai Y: Exendin-4, a glucagon‑like peptide‑1 receptor agonist, inhibits hyperglycemia‑induced apoptosis in myocytes by suppressing receptor for advanced glycation end products expression. Exp Ther Med 8: 1185-1190, 2014.
APA
Yi, B., Hu, X., Wen, Z., Zhang, T., & Cai, Y. (2014). Exendin-4, a glucagon‑like peptide‑1 receptor agonist, inhibits hyperglycemia‑induced apoptosis in myocytes by suppressing receptor for advanced glycation end products expression. Experimental and Therapeutic Medicine, 8, 1185-1190. https://doi.org/10.3892/etm.2014.1873
MLA
Yi, B., Hu, X., Wen, Z., Zhang, T., Cai, Y."Exendin-4, a glucagon‑like peptide‑1 receptor agonist, inhibits hyperglycemia‑induced apoptosis in myocytes by suppressing receptor for advanced glycation end products expression". Experimental and Therapeutic Medicine 8.4 (2014): 1185-1190.
Chicago
Yi, B., Hu, X., Wen, Z., Zhang, T., Cai, Y."Exendin-4, a glucagon‑like peptide‑1 receptor agonist, inhibits hyperglycemia‑induced apoptosis in myocytes by suppressing receptor for advanced glycation end products expression". Experimental and Therapeutic Medicine 8, no. 4 (2014): 1185-1190. https://doi.org/10.3892/etm.2014.1873
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