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Urocortin ameliorates diabetic cardiomyopathy in rats via the Akt/GSK-3β signaling pathway

  • Authors:
    • Xinyu Liu
    • Chunna Liu
    • Xiaoyan Zhang
    • Jiajun Zhao
    • Jin Xu
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Department of Pharmacology, Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China, Department of Endocrinology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 667-674
    |
    Published online on: January 23, 2015
       https://doi.org/10.3892/etm.2015.2211
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Abstract

Urocortin has been shown to exert powerful protective effects on various cardiovascular disease models. However, the role and mechanism of urocortin in protecting against diabetic cardiomyopathy (DCM) has not yet been elucidated. In the present study, the effects of urocortin on cardiac dysfunction, fibrosis, inflammation and the interrelated signaling pathways were investigated in a diabetic rat model. Diabetes mellitus (DM) was induced in the rats by intraperitoneal injection of streptozotocin. The diabetic rats were randomly divided into four groups: Diabetic control, urocortin, urocortin + astressin treatment and urocortin + triciribine treatment groups. All the experiments were conducted at 16 weeks following the induction of DM. The levels of glycosylated hemoglobin (HbA1c), creatine phosphokinase isoenzyme (CK‑MB) and plasma brain natriuretic peptide (BNP), as well as the myocardial collagen volume fraction (CVF) and left ventricular mass index (LVWI), were measured. In addition, levels of inflammatory factors, including transforming growth factor (TGF)‑β1, connective tissue growth factor (CTGF) and interrelated proteins, such as Akt and glycogen synthase kinase (GSK)‑3β, were detected by biochemical analyses. In the diabetic group, the levels of BNP and CK‑MB, as well as the mRNA and protein expression levels of TGF‑β1 and CTGF, and the LVWI and CVF, were higher compared with the rats in the control group (P<0.05). This was accompanied by decreased Akt and GSK‑3β phosphorylation (P<0.05). Notably, urocortin attenuated myocardial dysfunction, cardiac fibrosis and inflammation in the hearts of the diabetic rats. However, urocortin exhibited no effect on the level of HbA1c. In addition, the inhibited phosphorylation of Akt and GSK‑3β was restored with urocortin administration. However, all the effects of urocortin were eliminated with treatment of the corticotropin releasing factor receptor 2 antagonist, astressin. Triciribine, an Akt inhibitor, partially eliminated the effects of urocortin on myocardial dysfunction, inflammation and cardiac fibrosis in the hearts of the diabetic rats. These results indicated that urocortin may exhibit great therapeutic potential in the treatment of DCM by attenuating fibrosis and inflammation. Furthermore, the Akt/GSK‑3β signaling pathway may be partially involved in mediating these effects.
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1 

Jaffe AS, Spadaro JJ, Schechtman K, Roberts R, Geltman EM and Sobel BE: Increased conjestive heart failure after myocardial infarction of modest extent in patients with diatetes mellitus. Am Heart J. 108:31–37. 1984. View Article : Google Scholar : PubMed/NCBI

2 

Falcão-Pires I and Leite-Moreira AF: Diabetic cardiomyopathy: understanding the molecular and cellular basis to progress in diagnosis and treatment. Heart Fail Rev. 17:325–344. 2012. View Article : Google Scholar

3 

Huynh K, McMullen JR, Julius TL, Tan JW, Love JE, et al: Cardiac specific IGF-1 receptor transgenic expression protects against cardiac fibrosis and diastolic dysfunction in a mouse model of diabetic cardiomyopathy. Diabetes. 59:1512–1520. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Fang ZY, Prins JB and Marwick TH: Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications. Endocr Rev. 25:543–567. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Bujak M and Frangogiannis NG: The role of TGF-beta signaling in myocardial infarction and cardiac remodeling. Cardiovasc Res. 74:184–195. 2007. View Article : Google Scholar :

6 

Dai QM, Lu J and Liu NF: Fluvastatin attenuates myocardial interstitial fibrosis and cardiac dysfunction in diabetic rats by inhibiting over-expression of connective tissue growth factor. Chin Med J (Engl). 124:89–94. 2011.

7 

Vaughan J, Donaldson C, Bittencourt J, Perrin MH, Lewis K, Sutton S, et al: Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor. Nature. 378:287–292. 1995. View Article : Google Scholar : PubMed/NCBI

8 

Fekete EM and Zorrilla EP: Physiology, phamacology, and therapeutic relevance of urocortins in mammals: ancient CRF paralogs. Front Neuroendocrinol. 28:1–27. 2007. View Article : Google Scholar

9 

Honjo T, Inoue N, Shiraki R, Kobayashi S, Otsui K, Takahashi M, et al: Endothelial urocortin has potent antioxidative properties and is upregulated by inflammatory cytokines and pitavastatin. J Vasc Res. 43:131–138. 2006. View Article : Google Scholar

10 

Huang Y, Chan FL, Lau CW, Tsang SY, He GW, Chen ZY and Yao X: Urocortin-induced endothelium-dependent relaxation of rat coronary artery: role of nitric oxide and K+ channels. Br J Pharmacol. 135:1467–1476. 2002. View Article : Google Scholar : PubMed/NCBI

11 

Takahashi K: Distribution of urocortins and corticotropin-releasing factor receptors in the cardiovascular system. Int J Endocrinol. 2012:3952842012. View Article : Google Scholar : PubMed/NCBI

12 

Rademaker MT, Charles CJ, Espiner EA, Frampton CM, Lainchbury JG and Richards AM: Four-day urocortin-I administration has sustained beneficial haemodynamic, hormonal and renal effects in experimental heart failure. Eur Heart J. 26:2055–2062. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Liu CN, Yang C, Liu XY and Li S: In vivo protective effects of urocortin on ischemia-reperfusion injury in rat heart via free radical mechanisms. Can J Physiol Pharmacol. 83:459–465. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Yang C, Xu Y, Mendez T, Wang F, Yang Q and Li S: Effects of intravenous urocortin on angiotensin-coverting enzyme in rats. Vascul Pharmacol. 44:238–246. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Tarquini R, Lazzeri C, Pala L, Rotella CM and Gensini GF: The diabetic cardiomyopathy. Acta Diabetol. 48:173–181. 2011. View Article : Google Scholar

16 

Ma YX, Li WH and Xie Q: Rosuvastatin inhibits TGF-beta1 expression and alleviates myocardial fibrosis in diabetic rats. Pharmazie. 68:355–358. 2013.PubMed/NCBI

17 

Umezono T, Toyoda M, Kato M, Miyauchi M, et al: Glomerular espression of CTGF, TGF-beta 1 and type IV collagen in diabetic nephropathy. J Nephrol. 19:751–757. 2006.PubMed/NCBI

18 

Liu Y, Tanabe K, Baronnier D, Patel S, Woodgett J, et al: Conditional ablation of GSK-3β in islet beta cells results in expanded mass and resistance to fat feeding-induced diabetes in mice. Diabetologia. 53:2600–2610. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Wang Y, Feng W, Xue W, et al: Inactivation of GSK-3β by metallothionein prevents diabetes-related changes in cardiac energy metabolism, inflammation, nitrosative damage, and remodeling. Diabetes. 58:1391–1402. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Yu W, Wu J, Cai F, Xiang J, Zha W, et al: Curcumin alleviates diabetic cardiomyopathy in experimental diabetic rats. PloS One. 7:e520132012. View Article : Google Scholar : PubMed/NCBI

21 

Katare RG, Caporali A, Oikawa A, Meloni M, et al: Vitamin B1 analog benfotiamine prevents diabetes-induced diastolic dysfunction and heart failure through Akt/Pim-1-mediated survival pathway. Circ Heart Fail. 3:294–305. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Bale TL, Hoshijima M, Gu Y, et al: The cardiovascular physiologic actions of urocortin II: acute effects in murine heart failure. Proc Natl Acad Sci USA. 101:3697–3702. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Emeto TI, Moxon JV, Rush C, Woodward L and Golledge J: Relevance of urocortins to cardiovascular disease. J Mol Cell Cardiol. 51:299–307. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Liew HK, Hsu CW, Wang MJ, et al: Therapeutic benefit of urocortin in rats with intracerebral hemorrhage. J Neurosurg. 116:193–200. 2012. View Article : Google Scholar

25 

Rademaker MT, Charles CJ, Nicholls G and Richards M: Urocortin 2 sustains haemodynamic and renal function during introduction of beta-blockade in experimental heart failure. J Hypertens. 29:1787–1795. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Gruson D, Ginion A, Lause P, Ketelslegers JM, Thissen JP and Bertrand L: Urotensin II and urocortin trigger the expression of myostatin, a negative regulator of cardiac growth, in cardiomyocytes. Peptides. 33:351–353. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Rademaker MT, Charles CJ, Nicholls MG and Richards AM: Interactions of enhanced urocortin 2 and mineralocorticoid receptor antagonism in experimental heart failure. Circ Heart Fail. 6:825–832. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Parkes DG, Weisinger RS and May CN: Cardiovascular actions of CRH and urocortin: an update. Peptides. 22:821–827. 2001. View Article : Google Scholar : PubMed/NCBI

29 

Miki I, Seya K, Motomura S and Furukawa K: Role of corticotropin-releasing factor receptor type 2 in urocortin-induced vasodilation of rat aortas. J Pharmacol Sci. 96:170–176. 2004. View Article : Google Scholar : PubMed/NCBI

30 

Brar BK, Jonassen AK, Stephanou A, et al: Urocortin protects against ischemic and reperfusion injury via a MAPK-dependent pathway. J Biol Chem. 275:8508–8514. 2000. View Article : Google Scholar : PubMed/NCBI

31 

Rademaker MT, Charles CJ, Ellmers LJ, Lewis LK, Nicholls MG and Richards AM: Prolonged urocortin 2 administration in experimental heart failure: sustained hemodynamic, endocrine, and renal effects. Hypertension. 57:1136–1144. 2011. View Article : Google Scholar : PubMed/NCBI

32 

Ikeda K, Fujioka K, Manome Y and Tojo K: Clinical perspectives of urocortin and related agents for the treatment of cardiovascular disease. Int J Endocrinol. 2012:1986282012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liu X, Liu C, Zhang X, Zhao J and Xu J: Urocortin ameliorates diabetic cardiomyopathy in rats via the Akt/GSK-3β signaling pathway. Exp Ther Med 9: 667-674, 2015.
APA
Liu, X., Liu, C., Zhang, X., Zhao, J., & Xu, J. (2015). Urocortin ameliorates diabetic cardiomyopathy in rats via the Akt/GSK-3β signaling pathway. Experimental and Therapeutic Medicine, 9, 667-674. https://doi.org/10.3892/etm.2015.2211
MLA
Liu, X., Liu, C., Zhang, X., Zhao, J., Xu, J."Urocortin ameliorates diabetic cardiomyopathy in rats via the Akt/GSK-3β signaling pathway". Experimental and Therapeutic Medicine 9.3 (2015): 667-674.
Chicago
Liu, X., Liu, C., Zhang, X., Zhao, J., Xu, J."Urocortin ameliorates diabetic cardiomyopathy in rats via the Akt/GSK-3β signaling pathway". Experimental and Therapeutic Medicine 9, no. 3 (2015): 667-674. https://doi.org/10.3892/etm.2015.2211
Copy and paste a formatted citation
x
Spandidos Publications style
Liu X, Liu C, Zhang X, Zhao J and Xu J: Urocortin ameliorates diabetic cardiomyopathy in rats via the Akt/GSK-3β signaling pathway. Exp Ther Med 9: 667-674, 2015.
APA
Liu, X., Liu, C., Zhang, X., Zhao, J., & Xu, J. (2015). Urocortin ameliorates diabetic cardiomyopathy in rats via the Akt/GSK-3β signaling pathway. Experimental and Therapeutic Medicine, 9, 667-674. https://doi.org/10.3892/etm.2015.2211
MLA
Liu, X., Liu, C., Zhang, X., Zhao, J., Xu, J."Urocortin ameliorates diabetic cardiomyopathy in rats via the Akt/GSK-3β signaling pathway". Experimental and Therapeutic Medicine 9.3 (2015): 667-674.
Chicago
Liu, X., Liu, C., Zhang, X., Zhao, J., Xu, J."Urocortin ameliorates diabetic cardiomyopathy in rats via the Akt/GSK-3β signaling pathway". Experimental and Therapeutic Medicine 9, no. 3 (2015): 667-674. https://doi.org/10.3892/etm.2015.2211
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