اثر هشت هفته تمرین تناوبی شدید و مصرف کافئین بر بیان پروتئین p38α و HSP70 در کبد موش های صحرایی دیابتی شده با استرپتوزوتوسین

نوع مقاله : مقاله پژوهشی Released under (CC BY-NC 4.0) license I Open Access I

نویسندگان

1 کارشناس ارشد فیزیولوژی ورزشی، گروه تربیت‌بدنی و علوم ورزشی، دانشکاه علامه قزوینی ، قزوین، ایران

2 دانشیار گروه فیزیولوژی ورزشی، گروه تربیت‌بدنی و علوم ورزشی، دانشکده علوم اجتماعی، دانشگاه بین المللی امام خمینی(ره) ، قزوین، ایران

3 استادیار گروه فیزیولوژی ورزشی، گروه تربیت‌بدنی و علوم ورزشی، دانشکده علوم اجتماعی، دانشگاه بین المللی امام خمینی(ره) ، قزوین، ایران

4 گروه تربیتب بدنی و علوم ورزشی، دانشکده علوم تربیتی و روانشناسی، دانشگاه محقق اردبیلی، اردبیل، ایران

10.22049/jahssp.2022.27662.1445

چکیده

هدف: پروتئین‌هایی نظیر  p38αو  HSP70  از اهداف بالقوه درمان اختلالات دیابت نوع دو به ­شمار می­روند .هدف از این پژوهش بررسی هشت هفته تمرین تناوبی شدید و مصرف کافئین بر بیان پروتئین p38α و HSP70 در کبد موش‌های صحرایی دیابتی بود. روش­شناسی: در مطالعه‌ ‌تجربی حاضر، 50 سر موش صحرایی نر سفید نژاد ویستار با دامنۀ سنی 3-2 ماه به ‌طور تصادفی در 5 گروه 10 سری شامل: کنترل سالم(C)، کنترل دیابتی (D)، دیابتی تمرین کرده (D+T)، دیابتی دریافت کننده کافئین (D+CA) و دیابتی تمرین- کافئین (D+T+CA) تقسیم شدند. برنامه تمرین شامل 8 هفته و هفته‌ای 5 جلسه (6 تا 12 وهله 2 دقیقه‌ای با شدت 90- 85% سرعت بیشینه) بود و هر هفته پنج روز  70 mg/kg کافئین محلول با سالین تزریق شد. بـرای بررسـی پروتئین‌های p38α و HSP70 از روش وسترن بلات استفاده شد. داده‌ها با استفاده از آنالیز واریانس دوطرفه و در صورت مشاهده تفاوت معنادار آماری از آزمون توکی جهت تعیین اختلاف بین گروهی استفاده شـد  .یافته: سطح پروتئین HSP70 در موش‌های سالم و دیابتی با هم اختلاف معنادار داشت. تمرین تناوبی شدید و مصرف کافئین موجب افزایش معنادار  پـروتئین   HSP70نسبت به گروه  مکمل+ دیابتی شـد (001/0P=). گروه تمرین+ مکمل اثرگذاری بیشتری در افزایش  p38αنسبت به سایر گروه‌های دیابتی داشت، اما این تفاوت معنادار نبود (96/0P=). نتیجه‌گیری: تمرینات تناوبی شدید و مصرف کافئین با افزایش بیان HSP70 کبد می‌تواند نقشی مؤثری در مقابله با آسیب دیابت داشته باشد. با این حال، تمرینات تناوبی شدید و مصرف کافئین تاثیری بر بیان p38α  در کبد موش‌های صحرایی دیابتی ندارد.

کلیدواژه‌ها

موضوعات

عنوان مقاله [English]

The Effect of Eight-Week High Intensity Interval Training (HIIT) and Caffeine Intake On The p38α and hsp70 Protein expression in liver in Diabetic rats induced streptozotocin

نویسندگان [English]

  • Marya Rahmani 1
  • Abbas Sadeghi 2
  • Hassan Pourrazi 3
  • Seyed Hamed Ghiyami 4
1 MSc, , Department of Physical Education and Sports Science, Allameh Qazvini University, Qazvin, Iran
2 Associate Professor, Department of Physical Education and Sports Science, Faculty of Social Sciences, Imam Khomeini International University, Qazvin, Iran
3 Assistant Professor, Department of Physical Education and Sports Science, Faculty of Social Sciences, Imam Khomeini International University, Qazvin, Iran.
4 PhD student of Exercise Physiology, Department of Physical Education and Sports Science, Faculty of Educational Sciences and Psychology, Mohaghegh Ardabili University, Ardabil, Iran.
چکیده [English]

Aim:  Proteins such as p38α and HSP70 are considered as potential factors for type 2 diabetes disorders treatment. The aim of this study was to evaluate eight weeks of High-intensity Interval Training and caffeine consumption on p38α and HSP70 protein expression in the liver of diabetic rats. Method: 50 male Wistar rats with an age range of 2-3 months were randomly divided into 5 groups of 10 rats in each group: Healthy control (C), Diabetic control (D), Diabetic with Training (D+T), Diabetic with Caffeine treatment (D+CA), and Diabetic with Training and Caffeine treatment (D+ T + CA). The training program consisted of 8 sessions and 5 sessions per week (6 to 12 2-minute sessions with an intensity of 85-90% of maximum speed) and 70 mg / kg of Caffeine soluble with saline was injected every day for five days. Western blotting was used to evaluate p38α and HSP70 proteins. Data were analyzed using two-way analysis of variance and if a statistically significant difference was observed, Turkey test was used to determine the location of intergroup differences. Results:  HSP70 protein levels were significantly different in healthy and diabetic mice. High-intensity Interval Training and caffeine consumption significantly increased HSP70 protein compared to the supplement + diabetic group (P=0.001). exercise + supplement group had a greater effect on increasing p38α than other diabetic groups, but this difference was not significant (P=0.96).Conclusion:  High-intensity interval training and caffeine can play an effective role in counteracting damage of diabetes by increasing the expression of HSP70 in the liver.  However, high-intensity Interval Training and caffeine consumption have no effect on p38α expression in the liver of diabetic rats.
                 

کلیدواژه‌ها [English]

  • High-intensity Interval
  • Caffeine
  • Diabetes
  • p38α
  • HSP70

   

 

This is an open access article distributed under the following Creative Commons license: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

مراجع

  1. Palizvzn M, Khademi S, Ghazavi A, Mosayebi G. Correlation of two way active avoidance learning with Nitric Oxide and Ferric reduction/antioxidant power in rats. Journal of Arak University of Medical Sciences. 2006;9(4):1-8.
  2. Kennedy AL, Lyons TJ. Glycation, oxidation, and lipoxidation in the development of diabetic complications. Metabolism. 1997;46:14-21.
  3. Schrauwen-Hinderling V, Schrauwen P, Hesselink M, Van Engelshoven J, Nicolay K, Saris W, et al. The increase in intramyocellular lipid content is a very early response to training. The Journal of Clinical Endocrinology & Metabolism. 2003;88(4):1610-6.
  4. Adhikary L, Chow F, Nikolic-Paterson DJ, Stambe C, Dowling J, Atkins RC, et al. Abnormal p38 mitogen-activated protein kinase signalling in human and experimental diabetic nephropathy. Diabetologia. 2004;47(7):1210-22.
  5. Nasirian F, Dadkhah M, Moradi-Kor N, Obeidavi Z. Effects of Spirulina platensis microalgae on antioxidant and anti-inflammatory factors in diabetic rats. Diabetes, metabolic syndrome and obesity: targets and therapy. 2018;11:375. [In Persian]
  6. Benjamin IJ, McMillan DR. Stress (heat shock) proteins: molecular chaperones in cardiovascular biology and disease. Circulation research. 1998;83(2):117-32.
  7. Kurucz I, Morva A, Vaag A, Eriksson K-F, Huang X, Groop L, et al. Decreased expression of heat shock protein 72 in skeletal muscle of patients with type 2 diabetes correlates with insulin resistance. Diabetes. 2002;51(4):1102-9.
  8. Højlund K, Wrzesinski K, Larsen PM, Fey SJ, Roepstorff P, Handberg A, et al. Proteome analysis reveals phosphorylation of ATP synthase β-subunit in human skeletal muscle and proteins with potential roles in type 2 diabetes. Journal of Biological Chemistry. 2003;278(12):10436-42.
  9. Mulyani WRW, Sanjiwani MID, Sandra I, Lestari AAW, Wihandani DM, Suastika K, et al. Chaperone-based therapeutic target innovation: Heat shock protein 70 (HSP70) for Type 2 diabetes mellitus. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2020;13:559.
  10. Murphy LO, Blenis J. MAPK signal specificity: the right place at the right time. Trends in biochemical sciences. 2006;31(5):268-75.
  11. Wang S, Ding L, Ji H, Xu Z, Liu Q, Zheng Y. The role of p38 MAPK in the development of diabetic cardiomyopathy. International journal of molecular sciences. 2016;17(7):1037.
  12. Jing Y, Liu W, Cao H, Zhang D, Yao X, Zhang S, et al. Hepatic p38α regulates gluconeogenesis by suppressing AMPK. Journal of hepatology. 2015;62(6):1319-27.
  13. Bengal E, Aviram S, Hayek T. P38 mapk in glucose metabolism of skeletal muscle: beneficial or harmful? International Journal of Molecular Sciences. 2020;21(18):6480.
  14. Gehart H, Kumpf S, Ittner A, Ricci R. MAPK signalling in cellular metabolism: stress or wellness? EMBO reports. 2010;11(11):834-40.
  15. Thandavarayan RA, Watanabe K, Ma M, Gurusamy N, Veeraveedu PT, Konishi T, et al. Dominant-negative p38α mitogen-activated protein kinase prevents cardiac apoptosis and remodeling after streptozotocin-induced diabetes mellitus. American Journal of Physiology-Heart and Circulatory Physiology. 2009;297(3):H911-H9.
  16. Wilmer WA, Dixon CL, Hebert C. Chronic exposure of human mesangial cells to high glucose environments activates the p38 MAPK pathway. Kidney international. 2001;60(3):858-71.
  17. Zarghami Kamaneh A, Pashaei Z. The Effect of Medium-And High-Dose of Caffeine (1, 3, 7-Trimethylxanthine) Intake on Cardiovascular Factors Response at Baseline and Following One-Bout Aerobic Exercise. Journal of Applied Health Studies in Sport Physiology. 2019;6(2):25-31.. [In Persian]
  18. Mandel H. Update on caffeine consumption, disposition and action. Food and Chemical Toxicology. 2002;40(9):1231-4.
  19. Modi AA, Feld JJ, Park Y, Kleiner DE, Everhart JE, Liang TJ, et al. Increased caffeine consumption is associated with reduced hepatic fibrosis. Hepatology. 2010;51(1):201-9.
  20. Duarte JM, Agostinho PM, Carvalho RA, Cunha RA. Caffeine consumption prevents diabetes-induced memory impairment and synaptotoxicity in the hippocampus of NONcZNO10/LTJ mice. PLoS one. 2012;7(4):e21899.
  21. Lv X, Chen Z, Li J, Zhang L, Liu H, Huang C, et al. Caffeine protects against alcoholic liver injury by attenuating inflammatory response and oxidative stress. Inflammation Research. 2010;59(8):635-45.
  22. Saiki S, Sasazawa Y, Imamichi Y, Kawajiri S, Fujimaki T, Tanida I, et al. Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K inhibition. Autophagy. 2011;7(2):176-87.
  23. Li A, Wu N, Zou H, Zhu B, Xiong S, Xiao G. Low concentration of caffeine inhibits cell viability, migration and invasion, and induces cell apoptosis of B16F10 melanoma cells. Int J Clin Exp Pathol. 2016;9(11):11206-13.
  24. Nakaso K, Ito S, Nakashima K. Caffeine activates the PI3K/Akt pathway and prevents apoptotic cell death in a Parkinson's disease model of SH-SY5Y cells. Neuroscience letters. 2008;432(2):146-50.
  25. Paulsen G, Hanssen K, Rønnestad B, Kvamme N, Ugelstad I, Kadi F, et al. Strength training elevates HSP27, HSP70 and αB-crystallin levels in musculi vastus lateralis and trapezius. European journal of applied physiology. 2012;112(5):1773-82.
  26. Ogawa K, Sanada K, Machida S, Okutsu M, Suzuki K. Resistance exercise training-induced muscle hypertrophy was associated with reduction of inflammatory markers in elderly women. Mediators of inflammation. 2010;2010.
  27. Watanabe K-i, Ma M, Hirabayashi K-i, Gurusamy N, Veeraveedu PT, Prakash P, et al. Swimming stress in DN 14-3-3 mice triggers maladaptive cardiac remodeling: role of p38 MAPK. American Journal of Physiology-Heart and Circulatory Physiology. 2007;292(3):H1269-H77.
  28. Thong FS, Derave W, Urso B, Kiens B, Richter EA. Prior exercise increases basal and insulin-induced p38 mitogen-activated protein kinase phosphorylation in human skeletal muscle. Journal of applied physiology (Bethesda, Md : 1985). 2003;94(6):2337-41.
  29. Geiger PC, Wright DC, Han D-H, Holloszy JO. Activation of p38 MAP kinase enhances sensitivity of muscle glucose transport to insulin. American Journal of Physiology-Endocrinology and Metabolism. 2005;288(4):E782-E8.
  30. Eslami Z, Mohammadnajad PanahKandi Y, Sharifian S, Eghbal Moghanlou A, Sheikh SR, Mirghani SJ. Evaluation of the effect of aerobic exercise on UCP1 and MAPK p38 heat factor gene expression in subcutaneous adipose tissue in male Wistar rats fed a high-fat diet. Feyz Journal of Kashan University of Medical Sciences. 2021;25(4):1020-30.
  31. Gibala MJ, McGee SL, Garnham AP, Howlett KF, Snow RJ, Hargreaves M. Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1α in human skeletal muscle. Journal of applied physiology. 2009;106(3):929-34.
  32. Reznick RM, Shulman GI. The role of AMP‐activated protein kinase in mitochondrial biogenesis. The Journal of physiology. 2006;574(1):33-9.
  33. Jafari A, Zarghami Khameneh A, Nikookheslat S, Karimi P, Pashaei Z. Effects of Two Months of High Intensity Interval Training and Caffeine Supplementation on the Expression of Beclin-1 and Bcl-2 Proteins in the Myocardium of Type 2 Male Diabetic Rats. Journal of Applied Health Studies in Sport Physiology. 2021;8(2):83-91. [In Persian]
  34. Ebadi B, Damirchi A, Alamdari KA, Darbandi-Azar A, Naderi N. Cardiomyocyte mitochondrial dynamics in health and disease and the role of exercise training: A brief review. Research in Cardiovascular Medicine. 2018;7(3):107.. [In Persian]
  35. Sasidharan SR, Joseph JA, Anandakumar S, Venkatesan V, Ariyattu Madhavan CN, Agarwal A. An experimental approach for selecting appropriate rodent diets for research studies on metabolic disorders. BioMed research international. 2013;2013.
  36. Francis SH, Sekhar KR, Ke H, Corbin JD. Inhibition of cyclic nucleotide phosphodiesterases by methylxanthines and related compounds. Methylxanthines. 2011:93-133.
  37. Asgari Hazaveh D, Riyahi Malayeri S, Babaei S. Effect of eight weeks high intensity interval training and medium intensity interval training and Aloe vera intake on serum vaspin and insulin resistance in diabetic male rats. Journal of Arak University of Medical Sciences. 2018;20(11):67-75. [In Persian]
  38. Thomas C, Bishop D, Moore-Morris T, Mercier J. Effects of high-intensity training on MCT1, MCT4, and NBC expressions in rat skeletal muscles: influence of chronic metabolic alkalosis. American Journal of Physiology-Endocrinology and Metabolism. 2007;293(4):E916-E22.
  39. Farhadi H, Siahkohian M, Lotfali B, Pouran K. Effects of aerobic training and hypoxia on expression angiogenic factors in cardiac male Wistar rats. Journal of Sport in Biomotor Sciences. 2016;2(16):70-9. [In Persian]

 

  1. Nameni F. The Effect of a Single Bout Endurance Training on HSP70. World Applied Sciences Journal. 2012;19(2):211-4.
  2. Molanouri Shamsi M, Mahdavi M, Quinn LS, Gharakhanlou R, Isanegad A. Effect of resistance exercise training on expression of Hsp70 and inflammatory cytokines in skeletal muscle and adipose tissue of STZ-induced diabetic rats. Cell stress & chaperones. 2016;21(5):783-91. [In Persian]
  3. Moazami M, Bijeh N, Abbasian S. A Comparison of the Effects of Ramadan Fasting and Regular Aerobic Exercise on 70-Kda Heat Shock Protein (Hsp70), Lipid Profiles and Resistance Insulin in Non-Active Obese Men. Iranian Journal of Endocrinology and Metabolism. 2013;15(1):67-77. [In Persian]
  4. Mogharnasi M, TajiTabas A, Tashakorizadeh M, Nayebifar SH. The Effects of Resistance and Endurance Training on Levels of Nesfatin-1, HSP70, Insulin Resistance and Body Composition in Women with Type 2 Diabetes Mellitus. Science & Sports. 2019;34(1):e15-e23. [In Persian]
  5. tashakori zade m, mogharnasi m. A Study of the Effect of 10 Weeks of Resistance Training on HSP70 and Insulin Resistance in Type 2 Diabetic Women. Journal of Sport Biosciences. 2016;8(3):341-51. [In Persian]
  6. De Matos MA, de Oliveira Ottone V, Duarte TC, da Matta Sampaio PF, Costa KB, Fonseca CA, et al. Exercise reduces cellular stress related to skeletal muscle insulin resistance. Cell Stress and Chaperones. 2014;19(2):263-70.
  7. Gan SK, Samaras K, Thompson CH, Kraegen EW, Carr A, Cooper DA, et al. Altered myocellular and abdominal fat partitioning predict disturbance in insulin action in HIV protease inhibitor-related lipodystrophy. Diabetes. 2002;51(11):3163-9.
  8. Chung J. Nguyen AK, Henstridge DC, Holmes AG, Chan MH, Mesa JL, Lancaster GI, Southgate RJ, Bruce CR, Duffy SJ, Horvath I, Mestril R, Watt MJ, Hooper PL, Kingwell BA, Vigh L, Hevener A, Febbraio MA. HSP72 protects against obesity-induced insulin resistance Proc Natl Acad Sci USA. 2008;105:1739-44.
  9. Cangeri Di Naso F, Rosa Porto R, Sarubbi Fillmann H, Maggioni L, Vontobel Padoin A, Jacques Ramos R, et al. Obesity depresses the anti‐inflammatory HSP 70 pathway, contributing to NAFLD progression. Obesity. 2015;23(1):120-9.
  10. Silverstein MG, Ordanes D, Wylie AT, Files DC, Milligan C, Presley TD, et al. Inducing muscle heat shock protein 70 improves insulin sensitivity and muscular performance in aged mice. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences. 2015;70(7):800-8.
  11. Rodrigues-Krause J, Krause M, O’Hagan C, De Vito G, Boreham C, Murphy C, et al. Divergence of intracellular and extracellular HSP72 in type 2 diabetes: does fat matter? Cell Stress and Chaperones. 2012;17(3):293-302.
  12. Archer AE, Von Schulze AT, Geiger PC. Exercise, heat shock proteins and insulin resistance. Philosophical Transactions of the Royal Society B: Biological Sciences. 2018;373(1738):20160529.
  13. Lee YH, Giraud J, Davis RJ, White MF. c-Jun N-terminal kinase (JNK) mediates feedback inhibition of the insulin signaling cascade. Journal of Biological Chemistry. 2003;278(5):2896-902.
  14. Chung J, Nguyen A-K, Henstridge DC, Holmes AG, Chan MS, Mesa JL, et al. HSP72 protects against obesity-induced insulin resistance. Proceedings of the National Academy of Sciences. 2008;105(5):1739-44.
  15. Morino S, Kondo T, Sasaki K, Adachi H, Suico MA, Sekimoto E, et al. Mild electrical stimulation with heat shock ameliorates insulin resistance via enhanced insulin signaling. PloS one. 2008;3(12):e4068.
  16. Sondermann H, Becker T, Mayhew M, Wieland F, Hartl F-U. Characterization of a receptor for heat shock protein 70 on macrophages and monocytes. 2000.
  17. Le JA DBRV, Henstridge D. Phun J Zhou Z Soleymani T Daraei P Sitz D Vergnes L. HSP72 is a mitochondrial stress sensor critical for parkin action, oxidative metabolism, and insulin sensitivity in skeletal muscle. Diabetes. 2014;63:1488-505.
  18. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. methods. 2001;25(4):402-8.
  19. Murlasits Z. Cutlip RG, Geronilla KB, Rao KM, Wonderlin WF, Alway SE. Resistance training increases heat shock protein levels in skeletal muscle of young and old rats Exp Gerontol. 2006;41:398-406.
  20. Al-Amin M, Kawasaki I, Gong J, Shim Y-H. Caffeine induces the stress response and up-regulates heat shock proteins in Caenorhabditis elegans. Mol Cells. 2016;39(2):163.
  21. Whitham M, Walker GJ, Bishop NC. Effect of caffeine supplementation on the extracellular heat shock protein 72 response to exercise. Journal of Applied Physiology. 2006;101(4):1222-7.
  22. Chiang DJ, Roychowdhury S, Bush K, McMullen MR, Pisano S, Niese K, et al. Adenosine 2A receptor antagonist prevented and reversed liver fibrosis in a mouse model of ethanol-exacerbated liver fibrosis. PLoS One. 2013;8(7):e69114.
  23. Kramer HF, Goodyear LJ. Exercise, MAPK, and NF-κB signaling in skeletal muscle. Journal of applied physiology. 2007;103(1):388-95.
  24. Somwar R, Perreault M, Kapur S, Taha C, Sweeney G, Ramlal T, et al. Activation of p38 mitogen-activated protein kinase alpha and beta by insulin and contraction in rat skeletal muscle: potential role in the stimulation of glucose transport. Diabetes. 2000;49(11):1794-800.
  25. Chambers MA, Moylan JS, Smith JD, Goodyear LJ, Reid MB. Stretch‐stimulated glucose uptake in skeletal muscle is mediated by reactive oxygen species and p38 MAP‐kinase. The Journal of physiology. 2009;587(13):3363-73.
  26. Choi J, Choi SY, Lee SY, Lee JY, Kim HS, Lee SY, et al. Caffeine enhances osteoclast differentiation and maturation through p38 MAP kinase/Mitf and DC-STAMP/CtsK and TRAP pathway. Cellular signalling. 2013;25(5):1222-7.
  27. Medicherla S, Wadsworth S, Cullen B, Silcock D, Ma JY, Mangadu R, et al. p38 MAPK inhibition reduces diabetes-induced impairment of wound healing. Diabetes, metabolic syndrome and obesity: targets and therapy. 2009;2:91.
  28. Zhang G, Li Y-P. p38β MAPK upregulates atrogin1/MAFbx by specific phosphorylation of C/EBPβ. Skeletal muscle. 2012;2(1):1-9.
مطالعات کاربردی تندرستی در فیزیولوژی ورزش
دوره 9، شماره 1
فروردین 1401
صفحه 83-99

فایل ها

سابقه مقاله

  • تاریخ دریافت: 24 بهمن 1400
  • تاریخ بازنگری: 12 اردیبهشت 1401
  • تاریخ پذیرش: 15 اردیبهشت 1401

هم رسانی

ارجاع به این مقاله

آمار