RSS-Feed abonnieren
DOI: 10.1055/a-0985-4332
Moderate-intensity Exercise Training in Sole and Simultaneous Forms with Insulin Ameliorates the Experimental Type 1 Diabetes-induced Intrinsic Apoptosis in Testicular Tissue
Publikationsverlauf
accepted 15. Juli 2019
Publikationsdatum:
22. Oktober 2019 (online)
Abstract
The aim of this study was to investigate the ameliorative effect of moderate-intensity exercise training in sole and simultaneous forms with insulin on experimental type 1 diabetes (T1D)-induced apoptosis. A total of 36 mature male Wistar rats were divided into six equally sized groups, including sedentary control (Con), moderate-intensity exercise training (E-sole), sedentary T1D-induced (D-sole), moderate-exercise-trained T1D-induced (DE), insulin-treated sedentary T1D-induced (DI) and exercise-trained, and insulin-treated T1D-induced (DEI) groups. The 6-week exercise training intervention was involved 30 min of moderate-intensity running on a treadmill once daily (5 days/week). Next, tubular differentiation (TDI) and spermiogenesis (SPI) indices were assessed. The Bcl-2, Bax and caspase-3 expressions were determined using RT-PCR, immunohistochemistry and western blot techniques. Finally, the TUNEL staining was used to analyze the apoptosis ratio. The moderate-intensity exercise training in the sole and when simultaneously considered with insulin (DEI) maintained testicular cellularity, up-regulated Bcl-2 expression, reduced Bax expression and ameliorated the diabetes-induced apoptosis. We failed to show remarkable alterations in caspase-3 mRNA and protein levels in the DE group versus D-sole animals. In conclusion, the moderate-intensity exercise training is able to potentially protect testicular cells from T1D-induced intrinsic apoptosis via up-regulating Bcl-2 and downregulating Bax expressions. Moreover, it amplifies the insulin-induced anti-apoptotic impacts.
-
References
- 1 Nna VU, Bakar ABA, Mohamed M. Diabetes mellitus-induced male reproductive impairment: The role of natural products: A review. J Appl Pharm Sci 2017; 7: 233-242
- 2 Eizirik DL, Colli ML, Ortis F. The role of inflammation in insulitis and beta-cell loss in type 1 diabetes. Nat Rev Endocrinol 2009; 5: 219-226
- 3 Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 2003; 52: 102-110
- 4 Shaikh H, Shrivastava VK. Amir M. Diabetes mellitus and impairment of male reproductive function: Role of hypothalamus pituitary testicular axis and reactive oxygen species. Iran J Diabetes Obes 2016; 8
- 5 Shi GJ, Li ZM, Zheng J, Chen J, Han XX, Wu J, Li GY, Chang Q, Li YX, Yu JQ. Diabetes associated with male reproductive system damages: Onset of presentation, pathophysiological mechanisms and drug intervention. Biomed Pharmacother 2017; 90: 562-574
- 6 Jangir RN, Jain GC. Diabetes mellitus induced impairment of male reproductive functions: A review. Curr Diabetes Rev 2014; 10: 147-157
- 7 Arikawe AP, Daramola AO, Odofin AO, Obika LF. Alloxan-induced and insulin-resistant diabetes mellitus affect semen parameters and impair spermatogenesis in male rats. Afr J Reprod Health 2006; 10: 106-113
- 8 Alves MG, Martins AD, Cavaco JE, Socorro S, Oliveira PF. Diabetes, insulin-mediated glucose metabolism and sertoli/blood-testis barrier function. Tissue Barriers 2013; 1: e23992
- 9 Schoeller EL, Schon S, Moley KH. The effects of type 1 diabetes on the hypothalamic, pituitary and testes axis. Cell Tissue Res 2012; 349: 839-847
- 10 Shalaby MA, Hamowieh AR. Safety and efficacy of Zingiber officinale roots on fertility of male diabetic rats. Food Chem Toxicol 2010; 48: 2920-2924
- 11 Long L, Wang J, Lu X, Xu Y, Zheng S, Luo C, Li Y. Protective effects of scutellarin on type II diabetes mellitus-induced testicular damages related to reactive oxygen species/Bcl-2/Bax and reactive oxygen species/microcirculation/staving pathway in diabetic rat. J Diabetes Res 2015; 2015: 252530
- 12 Zhao Y, Song W, Wang Z, Wang Z, Jin X, Xu J, Bai L, Li Y, Cui J, Cai L. Resveratrol attenuates testicular apoptosis in type 1 diabetic mice: Role of Akt-mediated Nrf2 activation and p62-dependent Keap1 degradation. Redox Biol 2018; 14: 609-617
- 13 Shaha C, Tripathi R, Mishra DP. Male germ cell apoptosis: Regulation and biology. Philos Trans R Soc Lond B Biol Sci 2010; 365: 1501-1515
- 14 Danial NN. BCL-2 family proteins: critical checkpoints of apoptotic cell death. Clin Cancer Res 2007; 13: 7254-7263
- 15 Pellegrini M, Strasser A. Caspases, Bcl-2 family proteins and other components of the death machinery: Their role in the regulation of the immune response. 2013 https://www.ncbi.nlm.nih.gov/books/NBK6432/
- 16 Huang CY, Yang AL, Lin YM, Wu FN, Lin JA, Chan YS, Tsai FJ, Tsai CH, Kuo CH, Lee SD. Anti-apoptotic and pro-survival effects of exercise training on hypertensive hearts. J Appl Physiol (1985) 2012; 112: 883-891
- 17 Kim Y, Triolo M, Hood DA. Impact of aging and exercise on mitochondrial quality control in skeletal muscle. Oxid Med Cell Longev 2017; 2017: 3165396
- 18 Ko I-G, Kim S-E, Kim C-J, Jee Y-S. Treadmill exercise alleviates aging-induced apoptosis in rat cardiac myocytes. Int J Gerontol 2013; 7: 152-157
- 19 Chicco AJ, Schneider CM, Hayward R. Exercise training attenuates acute doxorubicin-induced cardiac dysfunction. J Cardiovasc Pharmacol 2006; 47: 182-189
- 20 Vina J, Sanchis-Gomar F, Martinez-Bello V, Gomez-Cabrera MC. Exercise acts as a drug; The pharmacological benefits of exercise. Br J Pharmacol 2012; 167: 1-12
- 21 Kwak HB. Effects of aging and exercise training on apoptosis in the heart. J Exerc Rehabil 2013; 9: 212-219
- 22 Hajizadeh Maleki B, Tartibian B. Long-term Low-to-Intensive cycling training: Impact on semen parameters and seminal cytokines. Clin J Sport Med 2015; 25: 535-540
- 23 Vaamonde D, Da Silva-Grigoletto ME, Garcia-Manso JM, Barrera N, Vaamonde-Lemos R. Physically active men show better semen parameters and hormone values than sedentary men. Eur J Appl Physiol 2012; 112: 3267-3273
- 24 Chigurupati S, Son TG, Hyun DH, Lathia JD, Mughal MR, Savell J, Li SC, Nagaraju GP, Chan SL, Arumugam TV, Mattson MP. Lifelong running reduces oxidative stress and degenerative changes in the testes of mice. J Endocrinol 2008; 199: 333-341
- 25 Gaskins AJ, Afeiche MC, Hauser R, Williams PL, Gillman MW, Tanrikut C, Petrozza JC, Chavarro JE. Paternal physical and sedentary activities in relation to semen quality and reproductive outcomes among couples from a fertility center. Hum Reprod 2014; 29: 2575-2582
- 26 Zhao X, Bian Y, Sun Y, Li L, Wang L, Zhao C, Shen Y, Song Q, Qu Y, Niu S, Wu W, Gao F. Effects of moderate exercise over different phases on age-related physiological dysfunction in testes of SAMP8 mice. Exp Gerontol 2013; 48: 869-880
- 27 Manna I, Jana K, Samanta PK. Effect of intensive exercise-induced testicular gametogenic and steroidogenic disorders in mature male Wistar strain rats: A correlative approach to oxidative stress. Acta Physiol Scand 2003; 178: 33-40
- 28 Tartibian B, Maleki BH. Correlation between seminal oxidative stress biomarkers and antioxidants with sperm DNA damage in elite athletes and recreationally active men. Clin J Sport Med 2012; 22: 132-139
- 29 Wise LA, Cramer DW, Hornstein MD, Ashby RK, Missmer SA. Physical activity and semen quality among men attending an infertility clinic. Fertil Steril 2011; 95: 1025-1030
- 30 Ryan AS. Exercise in aging: its important role in mortality, obesity and insulin resistance. Aging health 2010; 6: 551-563
- 31 Harriss DJ, Macsween A, Atkinson G. Standards for ethics in sport and exercise science research: 2018 update. Int J Sports Med 2017; 38: 1126-1131
- 32 Somboonwong J, Traisaeng S, Saguanrungsirikul S. Moderate-intensity exercise training elevates serum and pancreatic zinc levels and pancreatic ZnT8 expression in streptozotocin-induced diabetic rats. Life Sci 2015; 139: 46-51
- 33 Grant CW, Duclos SK, Moran-Paul CM, Yahalom B, Tirabassi RS, Arreaza-Rubin G, Spain LM, Guberski DL. Development of standardized insulin treatment protocols for spontaneous rodent models of type 1 diabetes. Comp Med 2012; 62: 381-390
- 34 Hoydal MA, Wisloff 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; 14: 753-760
- 35 Moshari S, Nejati V, Najafi G, Razi M. Insight into curcumin nanomicelle-induced derangements in male reproduction potential: An experimental study. Andrologia 2018; 50 doi:10.1111/and.12842. Epub 2017 Oct 23
- 36 Moshari S, Nejati V, Najafi G, Razi M. Nanomicelle curcumin-induced DNA fragmentation in testicular tissue; Correlation between mitochondria dependent apoptosis and failed PCNA-related hemostasis. Acta Histochem 2017; 119: 372-381
- 37 Zhao Y, Tan Y, Dai J, Li B, Guo L, Cui J, Wang G, Shi X, Zhang X, Mellen N, Li W, Cai L. Exacerbation of diabetes-induced testicular apoptosis by zinc deficiency is most likely associated with oxidative stress, p38 MAPK activation, and p53 activation in mice. Toxicol Lett 2011; 200: 100-106
- 38 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265-275
- 39 Zhao H, Xu S, Wang Z, Li Y, Guo W, Lin C, Gong S, Li C, Wang G, Cai L. Repetitive exposures to low-dose X-rays attenuate testicular apoptotic cell death in streptozotocin-induced diabetes rats. Toxicol Lett 2010; 192: 356-364
- 40 Kannan K, Jain SK. Oxidative stress and apoptosis. Pathophysiology 2000; 7: 153-163
- 41 Susnow N, Zeng L, Margineantu D, Hockenbery DM. Bcl-2 family proteins as regulators of oxidative stress. Semin Cancer Biol 2009; 19: 42-49
- 42 Khavarimehr M, Nejati V, Razi M, Najafi G. Ameliorative effect of omega-3 on spermatogenesis, testicular antioxidant status and preimplantation embryo development in streptozotocin-induced diabetes in rats. Int Urol Nephrol 2017; 49: 1545-1560
- 43 Giugliano D, Ceriello A, Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care 1996; 19: 257-267
- 44 Lee HB, Yu MR, Yang Y, Jiang Z, Ha H. Reactive oxygen species-regulated signaling pathways in diabetic nephropathy. J Am Soc Nephrol 2003; 14: S241-S245
- 45 Maiese K, Morhan SD, Chong ZZ. Oxidative stress biology and cell injury during type 1 and type 2 diabetes mellitus. Curr Neurovasc Res 2007; 4: 63-71
- 46 Shi GJ, Zheng J, Wu J, Qiao HQ, Chang Q, Niu Y, Sun T, Li YX, Yu JQ. Beneficial effects of Lycium barbarum polysaccharide on spermatogenesis by improving antioxidant activity and inhibiting apoptosis in streptozotocin-induced diabetic male mice. Food Funct 2017; 8: 1215-1226
- 47 Rashid K, Sil PC. Curcumin ameliorates testicular damage in diabetic rats by suppressing cellular stress-mediated mitochondria and endoplasmic reticulum-dependent apoptotic death. Biochim Biophys Acta 2015; 1852: 70-82
- 48 Wu XH, Yang SH, Duan DY, Cheng HH, Bao YT, Zhang Y. Anti-apoptotic effect of insulin in the control of cell death and neurologic deficit after acute spinal cord injury in rats. J Neurotrauma 2007; 24: 1502-1512
- 49 Barbieri E, Agostini D, Polidori E, Potenza L, Guescini M, Lucertini F, Annibalini G, Stocchi L, De Santi M, Stocchi V. The pleiotropic effect of physical exercise on mitochondrial dynamics in aging skeletal muscle. Oxid Med Cell Longev 2015; 2015: 917085
- 50 Aksoy Y, Yapanoglu T, Aksoy H, Demircan B, Oztasan N, Canakci E, Malkoc I. Effects of endurance training on antioxidant defense mechanisms and lipid peroxidation in testis of rats. Arch Androl 2006; 52: 319-323
- 51 Ji LL. Antioxidant signaling in skeletal muscle: A brief review. Exp Gerontol 2007; 42: 582-593
- 52 Cheng SM, Ho TJ, Yang AL, Chen IJ, Kao CL, Wu FN, Lin JA, Kuo CH, Ou HC, Huang CY, Lee SD. 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; 167: 478-485
- 53 Frances DE, Ronco MT, Monti JA, Ingaramo PI, Pisani GB, Parody JP, Pellegrino JM, Sanz PM, Carrillo MC, Carnovale CE. Hyperglycemia induces apoptosis in rat liver through the increase of hydroxyl radical: new insights into the insulin effect. J Endocrinol 2010; 205: 187-200
- 54 Koh PO. Streptozotocin-induced diabetes increases apoptosis through JNK phosphorylation and Bax activation in rat testes. J Vet Med Sci 2007; 69: 969-971
- 55 Tuncdemir M, Ozturk M. Regulation of the Ku70 and apoptosis-related proteins in experimental diabetic nephropathy. Metabolism 2016; 65: 1466-1477
- 56 Kwak HB, Song W, Lawler JM. Exercise training attenuates age-induced elevation in Bax/Bcl-2 ratio, apoptosis, and remodeling in the rat heart. FASEB J 2006; 20: 791-793
- 57 Quindry JC, Miller L, McGinnis G, Kliszczewicz B, Irwin JM, Landram M, Urbiztondo Z, Nanayakkara G, Amin R. Ischemia reperfusion injury, KATP channels, and exercise-induced cardioprotection against apoptosis. J Appl Physiol (1985) 2012; 113: 498-506
- 58 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; 105: 1934-1943
- 59 Elmore S. Apoptosis: A review of programmed cell death. Toxicol Pathol 2007; 35: 495-516
- 60 Kitazumi I, Tsukahara M. Regulation of DNA fragmentation: The role of caspases and phosphorylation. FEBS J 2011; 278: 427-441