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. 2016;8(1):26-33.
doi: 10.15171/jcvtr.2016.05. Epub 2016 Mar 14.

Cardiac Fibrosis and Down Regulation of GLUT4 in Experimental Diabetic Cardiomyopathy Are Ameliorated by Chronic Exposures to Intermittent Altitude

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Cardiac Fibrosis and Down Regulation of GLUT4 in Experimental Diabetic Cardiomyopathy Are Ameliorated by Chronic Exposures to Intermittent Altitude

Mahdi Faramoushi et al. J Cardiovasc Thorac Res. .
Free PMC article


Introduction: Chronic intermittent hypoxia is considered as a preconditioning status in cardiovascular health to inducing resistance to the low oxygen supply. Diabetic cardiomyopathy leads to inability of the heart to effective circulation of blood preventing of consequent tissue damages so; the aim of this study was elucidation of effect of chronic exposure to hypoxia on Cardiac fibrosis and expression of GLUT4 in experimental diabetic cardiomyopathy.

Methods: A total number of 30 rats were randomly divided into three groups; 1: Normoxia control group (NN, n = 10). 2: Normoxia diabetic group (ND, n = 10) that took fat diet for 2 weeks then were injected by streptozotocin (37 mg/kg) and 3: Hypoxia diabetic group (HD, n = 10): that were exposed to chronic intermittent hypoxia (CIH) (altitude ≈3400 m, 14% oxygen for 8 weeks). After hypoxia challenge, plasma metabolic parameters including: fasting blood glucose (FBS), triglyceride (TG) and total cholesterol (TC) were measured by colorimetric assay. Cardiac expression of GLUT4 protein and cardiac collagen accumulation were determined in the excised left ventricle by western blotting, and Masson trichrome staining respectively.

Results: Based on resultant data, FBS, TG and TC were significantly (P < 0.05) decreased in HD vs. ND. Homeostasis Model Assessment (HOMA) were also significantly attenuated after exposed to CIH in HD group compared to ND group (P < 0.05). Significant increase in packed cell volume and hemoglobin concentration was observed in HD group compared to ND group (P < 0.05). Comparison of heart wet weight between three groups showed a significant difference (P < 0.05) with lower amount in HD and ND versus NN. Myocardial fibrosis was significantly more pronounced in ND when compared to NN. Eight weeks exposure to hypoxia ameliorated this increase in HD group. Intermittent hypoxia significantly increased GLUT4 protein expression in HD compared to ND group (P < 0.05).

Conclusion: Data suggested that CIH might potentiate to improve glucose homeostasis and cardiac tissue structural damages created in type 2 diabetes (T2D).

Keywords: Altitude; Cardiac; Cardiomyopathy; Fibrosis; GLUT4.


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    1. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87(1):4–14. doi: 10.1016/j.diabres.2009.10.007. - DOI - PubMed
    1. Farag YM, Gaballa MR. Diabesity: an overview of a rising epidemic. Nephrol Dial Transplant. 2011;26(1):28–35. doi: 10.1093/ndt/gfq576‏. - DOI - PubMed
    1. Rubler S, Dlugash J, Yuceoglu YZ, Kumral T, Branwood AW, Grishman G. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol. 1972;30(6):595–602 ‏. - PubMed
    1. Gaster M, Staehr P, Beck-Nielsen H, Schrøder HD, Handberg A. GLUT4 is reduced in slow muscle fibers of type 2 diabetic patients: is insulin resistance in type 2 diabetes a slow, type 1 fiber disease? Diabetes. 2001;50(6):1324–1329‏. doi: 10.2337/diabetes.50.6.1324. - DOI - PubMed
    1. MacLean PS, Zheng D, Dohm GL. Muscle glucose transporter (GLUT 4) gene expression during exercise. Exerc Sport Sci Rev. 2000;28:148–152‏. - PubMed

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