Effect of 4 weeks high intensity interval training on gene expression of Ryanodine receptor calcium channels (RyR2), SERCA2a and Phospholamban in diabetic rat’s heart

Document Type : Research Paper

Authors

1 . Ph.D. Student of Exercise Physiology, Faculty of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran

2 Professor, Faculty of Physical Education and Sport Sciences, University of Tehran, Tehran, Iran

3 professor Faculty of Physical Education and Sport Sciences, University of Tehran, Tehran,Iran.

4 Assistant Professor, Faculty of Physical Education and Sport Sciences, Alzahra University, Tehran, Iran

Abstract

Diabetic cardiomyopathy (DCM) is one of the most important complications of diabetes and is one of the major causes of death in diabetic patients. DCM at the molecular level is rooted in down regulation of expression or activity of those various proteins involved in maintenance or regulation of intracellular calcium homeostasis. The aim of this study was to investigate the effect of 4 weeks of high intensity interval training (HIIT) on gene expression of calcium channel of ryanodine receptors (RyR2), SERCA2a and phospholamban (PLB) in the heart of diabetic male rats. In this experimental study, 24 male Wistar rats were divided into two groups: sedentary control and HIIT. Diabetes was induced in both groups by intraperitoneal injection of Streptozotocin (STZ) solution. 24 hours after the last training session, the rats were euthanized and their left ventricle was extracted. Real Time-PCR technique was used to determine the gene expression of RyR2, SERCA2a and PLB. To compare the two groups, independent t test was used at alpha level of 0.05. The results revealed that 4 weeks of HIIT significantly increased gene expression of RyR2 in the left ventricle of the heart of HIIT group (P=0.03). Although gene expression of SERCA2a and phospholamban increased, they were not significantly different. Based on these findings, it can be concluded that 4 weeks of HIIT could prevent and  minimize the maladjustments in these 2 proteins affecting cycle of cardiac contraction and reduce the risk of diabetic cardiomyopathy through increased RyR2 gene expression in the heart of diabetic rats.

Keywords


1.  Bidasee KR, Nallani K, Yu Y, Cocklin RR, Zhang Y, Wang M, et al. Chronic diabetes increases advanced glycation end products on cardiac ryanodine receptors/calcium-release channels. Diabetes. 2003;52(7):1825-36.
2.  Dincer UD. Cardiac ryanodine receptor in metabolic syndrome: is JTV519 (K201) future therapy? Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2012;5:89.
3.  Duan J, Zhang H-Y, Adkins SD, Ren BH, Norby FL, Zhang X, et al. Impaired cardiac function and IGF-I response in myocytes from calmodulin-diabetic mice: role of Akt and RhoA. American Journal of Physiology-Endocrinology And Metabolism. 2003;284(2):E366-E76.
4.  Shao C-H, Wehrens XH, Wyatt TA, Parbhu S, Rozanski GJ, Patel KP, et al. Exercise training during diabetes attenuates cardiac ryanodine receptor dysregulation. Journal of applied physiology. 2009;106(4):1280-92.
5.  Pereira L, Matthes J, Schuster I, Valdivia HH, Herzig S, Richard S, et al. Mechanisms of [Ca2+] i transient decrease in cardiomyopathy of db/db type 2 diabetic mice. Diabetes. 2006;55(3):608-15.
6.  Wisløff U, Støylen A, Loennechen JP, Bruvold M, Rognmo Ø, Haram PM, et al. Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study. Circulation. 2007;115(24):3086-94.
7.  Meyer P, Normandin E, Gayda M, Billon G, Guiraud T, Bosquet L, et al. High-intensity interval exercise in chronic heart failure: protocol optimization. Journal of cardiac failure. 2012;18(2):126-33.
8.  Lahaye SLD, Rebillard A, Zguira MS, Malardé L, Saïag B, Gratas-Delamarche A, et al. Effects of exercise training combined with insulin treatment on cardiac NOS1 signaling pathways in type 1 diabetic rats. Molecular and cellular biochemistry. 2011;347(1-2):53-62.
9.  Howarth FC, Almugaddum F, Qureshi M, Ljubisavijevic M. Effects of varying intensity exercise on shortening and intracellular calcium in ventricular myocytes from streptozotocin (STZ)-induced diabetic rats. Molecular and cellular biochemistry. 2008;317(1-2) :161.
10. Haram PM, Kemi OJ, Lee SJ, Bendheim MØ, Al-Share QY, Waldum HL, et al. Aerobic interval training vs. continuous moderate exercise in the metabolic syndrome of rats artificially selected for low aerobic capacity. Cardiovascular research. 2008;81.723-32:(4).
11. Guimaraes GV, Ciolac EG, Carvalho VO, D'Avila VM, Bortolotto LA, Bocchi EA. Effects of continuous vs. interval exercise training on blood pressure and arterial stiffness in treated hypertension. Hypertension Research. 2010;33(6):627.
12. Stølen TO, Høydal MA, Kemi OJ, Catalucci D, Ceci M, Aasum E, et al. Interval training normalizes cardiomyocyte function, diastolic Ca2+ control, and SR Ca2+ release synchronicity in a mouse model of diabetic cardiomyopathy. Circulation research. 2009;105; (527-636).
13. Hafstad AD, Lund J, Hadler-Olsen E, Höper AC, Larsen TS, Aasum E. High-and moderate-intensity training normalizes ventricular function and mechanoenergetics in mice with diet-induced obesity. Diabetes. 2013;62(7):2287-94.
14. Amatyakul S, Chakraphan D, Chotipaibulpan S, Patumraj S. Role of exercise training on pulpal blood flow in diabetic rats. Clinical hemorheology and microcirculation. 2006;34(1-2):295-301.
15. Sheikh AQ, Hurley JR, Huang W, Taghian T, Kogan A, Cho H, et al. Diabetes alters intracellular calcium transients in cardiac endothelial cells. PloS one. 2012;7(5):e36840.
16. Wang M, Zhang W-b, Zhu J-h, Fu G-s, Zhou B-q. Breviscapine ameliorates cardiac dysfunction and regulates the myocardial Ca 2+-cycling proteins in streptozotocin-induced diabetic rats. Acta diabetologica. 2010;47(1):209-18.
17. Rodrigues B, Cam MC, McNeill JH. Myocardial substrate metabolism: implications for diabetic cardiomyopathy. Journal of molecular and cellular cardiology. 1995;27(1):169-79.
18. Loganathan R, Bilgen M, Al-Hafez B, Zhero SV, Alenezy MD, Smirnova IV. Exercise training improves cardiac performance in diabetes: in vivo demonstration with quantitative cine-MRI analyses. Journal of Applied Physiology. 2007;102(2):665-72.
19. Harthmann AD, De Angelis K, Costa LP, Senador D, Schaan BD, Krieger EM, et al. Exercise training improves arterial baro-and chemoreflex in control and diabetic rats. Autonomic Neuroscience: Basic and Clinical. 2007;133(2):115-20.