Physical activity as a non-pharmacological and useful strategy in controlling of the apoptotic symptoms in diabetic model rats

Main Article Content

M. Bostani
S.A. Noaein


Background. In recent years, diabetes has become a global health problem. Apoptosis of pancreatic beta cells plays an important role in the pathogenesis of type 1 diabetes. Exercise as a non-pharmacological strategy to reduce the diabetic-induced complications has always been of interest to researchers. Therefore, the purpose of this study was to investigate the effect of aerobic exercise on levels of Bax, Bcl-2 and Bax/Bcl-2 ratio in pan­creatic tissue of streptozotocin (STZ)-induced diabetic rats. Materials and methods. A total number of 40 male Wistar rats (10 weeks old, 200–250 gr weight) were randomly divided into healthy control (HC), healthy trained (HT), diabetic control (DC), and diabetic trained (DT) groups. Diabetes was also induced by a single intraperitoneally injection of streptozocin (45 mg/kg). The training groups performed the exercise on the treadmill for five consecutive days within six weeks. The pancreatic tissue levels of the Bax and the Bcl-2 proteins were further determined via ELISA method. Results. The results showed that the induction of diabetes had significantly decreased the levels of Bcl-2 protein and increased the levels of Bax protein and Bax/Bcl-2 ratio in the pancreatic tissue (p < 0.05). As well, the findings showed that six weeks of aerobic exercise training had significantly increased the levels of Bcl-2 and significantly decreased the levels of Bax protein in DT group. Also, the Bax/Bcl-2 ratio reduced significantly in DT group (p < 0.05). The increase in displacement and transmission of apoptosis inducing factor (AIF) that have seen in oxidative stress status, is reduced in the tissues of trained individuals which indica­ting of the inhibition in the apoptotic signaling. Conclusions. According to the results of this study, exercise can be considered as an effective strategy to reduce the rate of diabetic-induced apoptosis and control its complications.

Article Details

How to Cite
Bostani, M., and S. Noaein. “Physical Activity As a Non-Pharmacological and Useful Strategy in Controlling of the Apoptotic Symptoms in Diabetic Model Rats”. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), vol. 16, no. 8, Apr. 2021, pp. 602-6, doi:10.22141/2224-0721.16.8.2020.222878.
Original Researches


Zhao L, Gu Q, Xiang L, et al. Curcumin inhibits apoptosis by modulating Bax/Bcl-2 expression and alleviates oxidative stress in testes of streptozotocin-induced diabetic rats. Ther Clin Risk Manag. 2017 Aug 28;13:1099-1105. doi:10.2147/TCRM.S141738.

Atkinson MA. ADA Outstanding Scientific Achievement Lecture 2004. Thirty years of investigating the autoimmune basis for type 1 diabetes: why can't we prevent or reverse this disease? Diabetes. 2005 May;54(5):1253-1263. doi:10.2337/diabetes.54.5.1253.

Kim KA, Lee MS. Recent progress in research on beta-cell apoptosis by cytokines. Front Biosci (Landmark Ed). 2009 Jan 1;14:657-664. doi:10.2741/3271.

Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol Rev. 2007 Jan;87(1):99-163. doi:10.1152/physrev.00013.2006.

Susnow N, Zeng L, Margineantu D, Hockenbery DM. Bcl-2 family proteins as regulators of oxidative stress. Semin Cancer Biol. 2009 Feb;19(1):42-49. doi:10.1016/j.semcancer.2008.12.002.

Raisova M, Hossini AM, et al. The Bax/Bcl-2 ratio determines the susceptibility of human melanoma cells to CD95/Fas-mediated apoptosis. J Invest Dermatol. 2001 Aug;117(2):333-340. doi:10.1046/j.0022-202x.2001.01409.x.

Youle RJ, Strasser A. The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 2008 Jan;9(1):47-59. doi:10.1038/nrm2308.

Wattenberg B, Lithgow T. Targeting of C-terminal (tail)-anchored proteins: understanding how cytoplasmic activities are anchored to intracellular membranes. Traffic. 2001 Jan;2(1):66-71. doi:10.1034/j.1600-0854.2001.20108.x.

Asa C, Maria S, Katharina SS, Bert A. Aquatic exercise is effective in improving exercise performance in patients with heart failure and type 2 diabetes mellitus. Evid Based Complement Alternat Med. 2012;2012:349209. doi:10.1155/2012/349209.

Selagzi H, Buyukakilli B, Cimen B, Yilmaz N, Erdogan S. Protective and therapeutic effects of swimming exercise training on diabetic peripheral neuropathy of streptozotocin-induced diabetic rats. J Endocrinol Invest. 2008 Nov;31(11):971-978. doi:10.1007/BF03345634.

Kadoglou NP, Vrabas IS, Kapelouzou A, et al. The impact of aerobic exercise training on novel adipokines, apelin and ghrelin, in patients with type 2 diabetes. Med Sci Monit. 2012 May;18(5):CR290-5. doi:10.12659/msm.882734.

Cheng SM, Ho TJ, Yang AL, et al. Exercise training enhances cardiac IGFI-R/PI3K/Akt and Bcl-2 family associated pro-survival pathways in streptozotocin-induced diabetic rats. Int J Cardiol. 2013 Jul 31;167(2):478-485. doi:10.1016/j.ijcard.2012.01.031.

Vsdna Nagesh S, Muniappan M, Kannan I, Viswanathan S. Erratum for Nagesh et al., phytochemical analysis and docking study of compounds present in a polyherbal preparation used in the treatment of dermatophytosis. Curr Med Mycol. 2018 Mar;4(1):34. doi:10.18502/cmm.4.1.33.

Høydal MA, Wisløff U, Kemi OJ, Ellingsen O. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. Eur J Cardiovasc Prev Rehabil. 2007 Dec;14(6):753-760. doi:10.1097/HJR.0b013e3281eacef1.

Chae CH, Jung SL, An SH, et al. Treadmill exercise improves cognitive function and facilitates nerve growth factor signaling by activating mitogen-activated protein kinase/extracellular signal-regulated kinase1/2 in the streptozotocin-induced diabetic rat hippocampus. Neuroscience. 2009 Dec 29;164(4):1665-1673. doi:10.1016/j.neuroscience.2009.09.075.

Devine PJ, Perreault SD, Luderer U. Roles of reactive oxygen species and antioxidants in ovarian toxicity. Biol Reprod. 2012 Feb 9;86(2):27. doi:10.1095/biolreprod.111.095224.

Agarwal A, Aponte-Mellado A, Premkumar BJ, Shaman A, Gupta S. The effects of oxidative stress on female reproduction: a review. Reprod Biol Endocrinol. 2012 Jun 29;10:49. doi:10.1186/1477-7827-10-49.

Nayki U, Onk D, Balci G, Nayki C, Onk A, Gunay M. The Effects of Diabetes Mellitus on Ovarian Injury and Reserve: An Experimental Study. Gynecol Obstet Invest. 2016;81(5):424-429. doi:10.1159/000442287.

Gomez-Cabrera MC, Viña J, Ji LL. Interplay of oxidants and antioxidants during exercise: implications for muscle health. Phys Sportsmed. 2009 Dec;37(4):116-1 23. doi:10.3810/psm.2009.12.1749.

Batista ML Jr, Rosa JC, Lopes RD, et al. Exercise training changes IL-10/TNF-alpha ratio in the skeletal muscle of post-MI rats. Cytokine. 2010 Jan;49(1):102-108. doi:10.1016/j.cyto.2009.10.007.

Siu PM, Bryner RW, Martyn JK, Alway SE. Apoptotic adaptations from exercise training in skeletal and cardiac muscles. FASEB J. 2004 Jul;18(10):1150-1152. doi:10.1096/fj.03-1291fje.

Fisher-Wellman K, Bloomer RJ. Acute exercise and oxidative stress: a 30 year history. Dyn Med. 2009 Jan 13;8:1. doi:10.1186/1476-5918-8-1.

Dejean LM, Martinez-Caballero S, Manon S, Kinnally KW. Regulation of the mitochondrial apoptosis-induced channel, MAC, by BCL-2 family proteins. Biochim Biophys Acta. 2006 Feb;1762(2):191-201. doi:10.1016/j.bbadis.2005.07.002.

Peterson JM, Bryner RW, Sindler A, Frisbee JC, Alway SE. Mitochondrial apoptotic signaling is elevated in cardiac but not skeletal muscle in the obese Zucker rat and is reduced with aerobic exercise. J Appl Physiol (1985). 2008 Dec;105(6):1934-1943. doi:10.1152/japplphysiol.00037.2008.

Fang J, Wu L, Chen L. Postconditioning attenuates cardiocyte ultrastructure injury and apoptosis by blocking mitochondrial permeability transition in rats. Acta Cardiol. 2008 Jun;63(3):377-387. doi:10.2143/AC.63.3.1020316.

García-Sáez AJ. The secrets of the Bcl-2 family. Cell Death Differ. 2012 Nov;19(11):1733-1740. doi:10.1038/cdd.2012.105.

Kwak HB. Effects of aging and exercise training on apoptosis in the heart. J Exerc Rehabil. 2013 Apr;9(2):212-219. doi:10.12965/jer.130002.

Vainshtein A, Kazak L, Hood DA. Effects of endurance training on apoptotic susceptibility in striated muscle. J Appl Physiol (1985). 2011 Jun;110(6):1638-1645. doi:10.1152/japplphysiol.00020.2011.

Bostani M, Rahmati M, Mard SA. The effect of endurance training on levels of LINC complex proteins in skeletal muscle fibers of STZ-induced diabetic rats. Sci Rep. 2020 May 26;10(1):8738. doi:10.1038/s41598-020-65793-5.