Effect of progressive aerobic training, injection of adipose tissue-derived stem cells, and their combination on Bax and Bcl-2 levels of beta - pancreatic cells in diabetic rats

authors:

avatar seyed hoseinbabaeesadati , * , avatar Abdolreza Jafari Chashmi , avatar Seyed AbdollahHashemvarzi

Koomesh: Vol.23, issue 2; 242-249
published online: May 02, 2021
article type: Research Article
received: April 02, 2020
accepted: September 02, 2020

how to cite: hoseinbabaeesadati S, Jafari Chashmi A, AbdollahHashemvarzi S. Effect of progressive aerobic training, injection of adipose tissue-derived stem cells, and their combination on Bax and Bcl-2 levels of beta - pancreatic cells in diabetic rats. koomesh. 2021;23(2):e153262. 

Abstract

Introduction: Apoptosis is protective cellular process the plays an important role in the development and homeostasis of natural tissue as well as disease-causing factors. Current study was accomplished in order to determine the effect of progressive aerobic training with injection of adipose tissue-derived stem cells Bax (as an apoptotic protein) and Bcl-2 (as an anti-apoptotic protein) and the ratio of Bax to Bcl-2 of beta-pancreatic cells in diabetic rats with streptozotocin. Materials and Methods: 48 rat’s adult rats were divided into 6 groups: control, sham, diabetes, exercise, stem cell and exercise +stem cell. Diabetes was induced by intraperitoneal injection of streptozotocin (60 mg/kg) dissolved in citrate buffer, with pH = 4.5. The exercise protocol was treadmill running for 5 days per week with intensity of 60-70% VO2max for 6 weeks. In the stem cell group, 5 ml PBS with 1.5 ×106 stem cells extracted from human adipose tissue of diabetic rats was injected into the tail vein. Levels of Bax and Bcl2 of beta pancreatic cells were measured by laboratory kit. Results: The findings showed that the levels of Bax and Bcl- 2 significanly increased and decreased in the diabetic grop than the control group, respectively (P< 0. 000).  Bax/Bcl-2 ratio also increased in the diabetic group than the control group. The diabetic groups treated with exercise, stem cells, and both exhibited signifiacly lower Bax and higher Bcl-2 levels than the diabetic group alone.  Moreover, in these groups Bax/Bcl-2 ratio was sigficanly lower than the diabetic group alone. Conclusion: It seems that exercise, stem - cell therapy and the combined treatement could prevent β-cell apoptosis.  

References

  • 1.

    Havilah P, Pandit Vinodh B, Durga Prasad K. Adenosine deaminase activity in Type-2 diabetes mellitus - an independent marker of glycemic status and stimulator of lipid peroxidation. Int J Chem Life Sci 2013; 02: 1175-1178.

  • 2.

    Eickhoff H, Guimaraes A, Louro TM, Seica RM, Sousa FC. Insulin resistance and beta cell function before and after sleeve gastrectomy in obese patients with impaired fasting glucose or type 2 diabetes. Surg Endo 2015; 29: 438-443.

  • 3.

    Zhang T, He H, Yang HL, Huang HJ, Zhang MF, An ZM, et al. [Study of glycated albumin cut-off point in diabetes mellitus and impaired glucose regulation]. Sichuan Da Xue Xue Bao Yi Xue Ban 2014; 45: 274-277.

  • 4.

    Krishna KA, Rao GV, Rao KS. Stem cell-based therapy for the treatment of Type 1 diabetes mellitus. Regen Med 2007; 2: 171-177.

  • 5.

    Yiu KH, Tse HF. Specific role of impaired glucose metabolism and diabetes mellitus in endothelial progenitor cell characteristics and function. Arterioscler Thromb Vasc Biol 2014; 34: 1136-1143.

  • 6.

    Sharma A, Ezekowitz JA. Diabetes, impaired fasting glucose, and heart failure: it's not all about the sugar. Euro J heart Failure 2014; 16: 1153-1156.

  • 7.

    Hu MJ, Ruan GP, Yao X, Ruan GH, Wang JX, Pang RQ, et al. Induced autologous stem cell transplantation for treatment of rabbit type 1 diabetes. Cell Biol Int 2013; 37: 624-632.

  • 8.

    Quadrilatero J, Bombardier E, Norris SM, Talanian JL, Palmer MS, Logan H, et al. Prolonged moderate-intensity aerobic exercise does not alter apoptotic signaling and DNA fragmentation in human skeletal muscle. Am J Physiol Endoc Metab 2010; 298: E534-E547.

  • 9.

    Favaloro B, Allocati N, GrazianoV, DiIlio C, De Laurenzi V. Role of apoptosis in disease. Aging (Albany NY) 2012; 4: 330.

  • 10.

    Kotrk S, Kayatekin BM, Resmi H, Akgz O, Kaynak C, zer E. The apoptotic response to strenuous exercise of the gastrocnemius and solues muscle fibers in rats. Eur J Appl Physiol 2008; 102: 515-524.

  • 11.

    Siu PM, Bryner RW, Martyn JK, Alway SE. Apoptotic adaptations from exercise training in skeletal and cardiac muscles. The FASEB J 2004; 18: 1150-1152.

  • 12.

    Noguchi H. Recent advances in stem cell research for the treatment of diabetes. World J Stem Cells 2009; 1: 36-42.

  • 13.

    Mimeault M, Batra SK. Recent progress on normal and malignant pancreatic stem/progenitor cell research: therapeutic implications for the treatment of type 1 or 2 diabetes mellitus and aggressive pancreatic cancer. Gut 2008; 57: 1456-1468.

  • 14.

    Moradi A, Mohammadi S, Hamidi Alamdari D. Effect of adipose tissue-derived stem cells on the control of the blood glucose level in diabetic rats. J Shahid Sadoughi Univ Med Sci 2015; 23: 717-726. (Persian).

  • 15.

    Krishna KA, Rao GV, Rao KS. Stem cell-based therapy for the treatment of Type 1 diabetes mellitus. Regene Med 2007; 2: 171-177.

  • 16.

    Lock LT, Tzanakakis ES. Stem/Progenitor cell sources of insulin-producing cells for the treatment of diabetes. Tissue Eng 2007; 13: 1399-1412.

  • 17.

    Guo F, Lv S, Lou Y, Tu W, Liao W, Wang Y, et al. Bone marrow stromal cells enhance the angiogenesis in ischaemic cortex after stroke: involvement of notch signalling. Cell Biol Int 2012; 36: 997-1004.

  • 18.

    De Salles Bf, Simo R, Fleck SJ, Dias I, Kraemer-Aguiar LG, Bouskela E. Effects of resistance training on cytokines. Int J Sports Med 2010; 31: 441-450.

  • 19.

    Tang Z, Yuan L, Gu C, Liu Y, Zhu L. Effect of exercise on the expression of adiponectin mRNA and GLUT4 mRNA in type 2 diabetic rats. J Huazhong Univ Sci Technol Med Sci 2005; 25: 191-193. (Persian).

  • 20.

    Eizadi M, Behboudi L. Effect of acute and chronic exercise on beta-cell function in diabetic patients. Knowledge Health 2012; 6: 15-19. (Persian).

  • 21.

    Adamopoulos S, Parissis J, Karatzas D, Kroupis C, Georgiadis M, Karavolias G, et al. Physical training modulates proinflammatory cytokines and the soluble Fas/soluble Fasligand system in patients with chronic heart failure. J Am Coll Cardiol 2002; 39: 653-663.

  • 22.

    Hong JH, Kim MJ, Park MR, Kwag OG, Lee IS, Byun BH, et al. Effects of vitamin E on oxidative stress and membrane fluidity in brain of streptozotocin-induced diabetic rats. Clin Chim Acta 2004; 340: 107-115.

  • 23.

    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 2008; 105: 1934-1943.

  • 24.

    Kotrk S, Kayatekin BM, Resmi H, Akgz O, Kaynak C, zer E. The apoptotic response to strenuous exercise of the gastrocnemius and solues muscle fibers in rats. Eur J Appl Physiol 2008; 102: 515-524.

  • 25.

    Siu PM, Bryner RW, Martyn JK, Alway SEApoptotic adaptations from exercise training in skeletal and cardiac muscles. The FASEB J 2004; 18: 1150-1152.

  • 26.

    Fang J, Wu L, Chen L. Postconditioning attenuates cardiocyte ultrastructure injury and apoptosis by blocking blocking mitochondrial permeability transition in rats. Acta Cardiol 2008; 63: 377-387.

  • 27.

    Marzetti E, Lawler JM, Hiona A, Manini T, Seo AY, Leeuwenburgh C. Modulation of age-induced apoptotic signaling and cellular remodeling by exercise and calorie restriction in skeletal muscle. Free Radic Biol Med 2008; 44: 160-168.

  • 28.

    Mauricio D MP, Orlinick JR, Vaishnam AK. Role of Fas-FasL in insulitis in nonobes diabetic mouse. Chin Med J 2018; 43: 1537-1547.

  • 29.

    Allen DA, Yaqoob MM, Harwood SM. Mechanisms of high glucose-induced apoptosis and its relationship to diabetic complications. J Nutr Biochem 2005; 16: 705-713.

  • 30.

    Mazzola PN, Terra M, Rosa AP, Mescka CP, Moraes TB, Piccoli B, et al. Regular exercise prevents oxidative stress in the brain of hyperphenylalaninemic rats. Metab Brain Dis 2011; 26: 291.

  • 31.

    Aboutaleb N, Shamsaei N, Khaksari M, Erfani S, Rajabi H, Nikbakht F. Pre-ischemic exercise reduces apoptosis in hippocampal CA3 cells after cerebral apoptosis in hippocampal CA3 cells after cerebral ischemia by modulation of the Bax/Bcl-2 proteins ratio and prevention of caspase-3 activation. J Physiol Sci 2015; 65: 435-443.

  • 32.

    Hong JH, Kim MJ, Park MR, Kwag OG, Lee IS, Byun BH, et al. Effects of vitamin E on oxidative stress and membrane fluidity in brain of streptozotocin-induced diabetic rats. Clin Chim Acta 2004; 340: 107-115.

  • 33.

    Capitelli CS, Lopes CS, Alves AC, Barbiero J, Oliveira LF, Silva VJ, et al. Opposite effects of bone marrow-derived cells transplantation in MPTP-rat model of Parkinson's disease: a comparison study of mononuclear and mesenchymal stem cells. Int J Med Sci 2014; 11: 1049-1064.

  • 34.

    Kang X, Huadong X, Sasa T, Xiaoyu Z, Zijun D, Li Z. Dopamine release from transplanted neural stem cells in Parkinsonian rat striatum in vivo. Pnas 2014; 111: 15804-15809.

  • 35.

    Hashemvarzi SA, Heidarianpour A. Preconditioning effect of aerobic exercise with D3 Vitamin consumption on VEGF levels in the 6-OHDA lesioned Parkinson's disease rat model. Sport Physiol 2016; 8: 129-142. (Persian).

  • 36.

    Lock LT, Tzanakakis ES. Stem/Progenitor cell sources of insulin-producing cells for the treatment of diabetes. Tissue Eng 2007; 13: 1399-1412.

  • 37.

    Zhao Y, Lin B, Dingeldein M, Guo C, Hwang D, Holterman MJ. New type of human blood stem cell: a double-edged sword for the treatment of type 1 diabetes. Transl Res 2010; 155: 211-216.