Daneshvar Medicine

Daneshvar Medicine

The effects of high-intensity interval training on TGF-β and HSP72 gene expression in kidney tissue and selective renal serum biomarkers of type-II diabetic rats

Document Type : Original Article

Authors
Mostafa Baranchi
Hamid Agha-Alinejad
Department of Exercise Physiology, Tarbiat Modares University, Tehran, Iran
10.22070/daneshmed.2021.14798.1100
Abstract
Background and Objective: Diabetic Kidney Disease (DKD) is one of the most significant complication of diabetes. Heat Shock Protein 72 (HSP72) and Transforming Growth Factor beta (TGF-β) are regarded as biomarkers for renoprotective strategies. High-intensity interval training (HIIT) may have beneficial effect on diabetes management. The purpose of the present study was to investigate the effects of HIIT on kidney expression of HSP72 and TGF-β in type-II diabetic (T2D) rats.
Materials and Methods: 21 rats were randomly divided into three groups as follows: control (Con), diabetic (Dibt), diabetic HIIT (Dibt-HIIT). Nicotinamide and streptozotocin were used intraperitoneally for diabetes induction. The Dibt-HIIT received four-week HIIT training. 24 hours following the last training session, all animals were anesthetized. Blood samples were collected for measuring the glucose, insulin, creatinine, urea and uric acid concentrations. The left kidney was removed and homogenized for measuring of HSP72 and TGF-βgene expression (through Real-Time PCR).
Results: Diabetes significantly increased gene expression of TGF-β and suppressed HSP-72 gene expression. Compared to Dibt group, HIIT decreased plasma glucose level but these changes were not significant. However, HIIT improved HOMA-IR (p=0.03). Creatinine change was not significant but Uric acid decreased in Dibt-HIIT group significantly (p=0.02).  Also, HIIT reduced kidney expression of TGF-β and increased HSP72 expression in Dibt-HIIT group (p=0.001).
Conclusion: Our findings indicated that HIIT, as a non-pharmacologic approach, may have protective effect on kidney of rats with T2D.
Keywords
High-intensity interval training
Type-II diabetes
Kidney
HSP72
TGFβ
  1. Rabkin R. Diabetic nephropathy. Clinical Cornerstone 2003;5(2):1–11.
  2. Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, et al. Chronic kidney disease: global dimension and perspectives. Lancet 2013;382(9888):260–72.
  3. Atalay M, Oksala N, Lappalainen J, Laaksonen DE, Sen CK, Roy S. Heat shock proteins in diabetes and wound healing. Current Protein & Peptide Science 2009;10(1):85–95.
  4. Danda RS, Habiba NM, Rincon-Choles H, Bhandari BK, Barnes JL, Abboud HE, et al. Kidney involvement in a nongenetic rat model of type 2 diabetes. Kidney International 2005;68(6):2562–71.
  5. Chebotareva N, Bobkova I, Shilov E. Heat shock proteins and kidney disease: perspectives of HSP therapy. Cell Stress Chaperones 2017;22(3):319–43.
  6. Barrera-Chimal J, Pérez-Villalva R, Cortés-González C, Ojeda-Cervantes M, Gamba G, Morales-Buenrostro LE, et al. HSP72 is an early and sensitive biomarker to detect acute kidney injury. EMBO Molecular Medicine 2011;3(1):5–20.
  7. Sharma K, McGowan TA. TGF-beta in diabetic kidney disease: role of novel signaling pathways. Cytokine & Growth Factor Reviews 2000;11(1–2):115–23.
  8. Meng X-M, Tang PM-K, Li J, Lan HY. TGF-β/Smad signaling in renal fibrosis. Frontiers in Physiology 2015;6:82.
  9. Ren L, Sen U, Pushpakumar S. Exercise training reduces TGF-β mediated epithelial mesenchymal transition in diabetic kidney. The FASEB Journal 2017;31(1_supplement):1086.5-1086.5.
  10. Chen S, Jim B, Ziyadeh FN. Diabetic nephropathy and transforming growth factor-beta: transforming our view of glomerulosclerosis and fibrosis build-up. Seminars in Nephrology 2003;23(6):532–43.
  11. Sharma K, Jin Y, Guo J, Ziyadeh FN. Neutralization of TGF- by Anti-TGF- Antibody Attenuates Kidney Hypertrophy and the Enhanced Extracellular Matrix Gene Expression in STZ-Induced Diabetic Mice. Diabetes 1996;45(4):522–30.
  12. Heiwe S, Jacobson SH. Exercise training for adults with chronic kidney disease. The Cochrane Database of Systematic Reviews 2011;(10):CD003236.
  13. Torma F, Gombos Z, Jokai M, Takeda M, Mimura T, Radak Z. High intensity interval training and molecular adaptive response of skeletal muscle. Sports Medicine and Health Science 2019;1(1):24–32.
  14. Cassidy S, Thoma C, Houghton D, Trenell MI. High-intensity interval training: a review of its impact on glucose control and cardiometabolic health. Diabetologia 2017;60(1):7–23.
  15. Liu J-X, Zhu L, Li P-J, Li N, Xu Y-B. Effectiveness of high-intensity interval training on glycemic control and cardiorespiratory fitness in patients with type 2 diabetes: a systematic review and meta-analysis. Aging Clinical and Experimental Research 2019;31(5):575–93.
  16. Larsen MO, Wilken M, Gotfredsen CF, Carr RD, Svendsen O, Rolin B. Mild streptozotocin diabetes in the Göttingen minipig. A novel model of moderate insulin deficiency and diabetes. American Journal of Physiology. Endocrinology and Metabolism 2002;282(6):E1342-1351.
  17. Dulin WE, Wyse BM. Reversal of streptozotocin diabetes with nicotinamide. Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) 1969;130(3):992–4.
  18. Masiello P, Broca C, Gross R, Roye M, Manteghetti M, Hillaire-Buys D, et al. Experimental NIDDM: development of a new model in adult rats administered streptozotocin and nicotinamide. Diabetes 1998;47(2):224–9.
  19. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010;33 Suppl 1:S62-69.
  20. Rio DC, Ares M, Hannon GJ, Nilsen TW. Purification of RNA using TRIzol (TRI reagent). Cold Spring Harbor Protocols 2010;2010(6):pdb.prot5439.
  21. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods (San Diego, Calif.) 2001;25(4):402–8.
  22. Remuzzi G, Schieppati A, Ruggenenti P. Nephropathy in Patients with Type 2 Diabetes. New England Journal of Medicine 2002;346(15):1145–51.
  23. Tufescu A, Kanazawa M, Ishida A, Lu H, Sasaki Y, Ootaka T, et al. Combination of exercise and losartan enhances renoprotective and peripheral effects in spontaneously type 2 diabetes mellitus rats with nephropathy. Journal of Hypertension 2008;26(2):312–21.
  24. De Nardi AT, Tolves T, Lenzi TL, Signori LU, Silva AMV da. High-intensity interval training versus continuous training on physiological and metabolic variables in prediabetes and type 2 diabetes: A meta-analysis. Diabetes Research and Clinical Practice 2018;137:149–59.
  25. Yang D, Yang Y, Li Y, Han R. Physical Exercise as Therapy for Type 2 Diabetes Mellitus: From Mechanism to Orientation. Annals of Nutrition & Metabolism 2019;74(4):313–21.
  26. Colberg SR, Sigal RJ, Yardley JE, Riddell MC, Dunstan DW, Dempsey PC, et al. Physical Activity/Exercise and Diabetes: A Position Statement of the American Diabetes Association. Diabetes Care 2016;39(11):2065–79.
  27. Gibala MJ, Little JP. Just HIT it! A time-efficient exercise strategy to improve muscle insulin sensitivity: Perspectives. The Journal of Physiology 2010;588(18):3341–2.
  28. Weston KS, Wisløff U, Coombes JS. High-intensity interval training in patients with lifestyle-induced cardiometabolic disease: a systematic review and meta-analysis. British Journal of Sports Medicine 2014;48(16):1227–34.
  29. Levin SR, Coburn JW, Abraira C, Henderson WG, Colwell JA, Emanuele NV, et al. Effect of intensive glycemic control on microalbuminuria in type 2 diabetes. Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type 2 Diabetes Feasibility Trial Investigators. Diabetes Care 2000;23(10):1478–85.
  30. Gillen JB, Little JP, Punthakee Z, Tarnopolsky MA, Riddell MC, Gibala MJ. Acute high-intensity interval exercise reduces the postprandial glucose response and prevalence of hyperglycaemia in patients with type 2 diabetes. Diabetes, Obesity and Metabolism 2012;14(6):575–7.
  31. Lee SS, Yoo JH, So YS. Effect of the low- versus high-intensity exercise training on endoplasmic reticulum stress and GLP-1 in adolescents with type 2 diabetes mellitus. Journal of Physical Therapy Science 2015;27(10):3063–8.
  32. Roberts CK, Little JP, Thyfault JP. Modification of insulin sensitivity and glycemic control by activity and exercise. Medicine and Science in Sports and Exercise 2013;45(10):1868–77.
  33. Ahmad AM. Moderate-intensity continuous training: is it as good as high-intensity interval training for glycemic control in type 2 diabetes? Journal of Exercise Rehabilitation 2019;15(2):327–33.
  34. Amri J, Parastesh M, Sadegh M, Latifi SA, Alaee M. High-intensity interval training improved fasting blood glucose and lipid profiles in type 2 diabetic rats more than endurance training; possible involvement of irisin and betatrophin. Physiology International 2019;106(3):213–24.
  35. Lappalainen J, Oksala NKJ, Laaksonen DE, Khanna S, Kokkola T, Kaarniranta K, et al. Suppressed heat shock protein response in the kidney of exercise-trained diabetic rats. Scandinavian Journal of Medicine & Science in Sports 2018;28(7):1808–17.
  36. Silva KA dos S, Luiz R da S, Rampaso RR, de Abreu NP, Moreira ÉD, Mostarda CT, et al. Previous exercise training has a beneficial effect on renal and cardiovascular function in a model of diabetes. PloS One 2012;7(11):e48826.
  37. Albright AL, Mahan JD, Ward KM, Sherman WM, Roehrig KL, Kirby TE. Diabetic nephropathy in an aerobically trained rat model of diabetes. Medicine and Science in Sports and Exercise 1995;27(9):1270–7.
  38. Rodrigues AM, Bergamaschi CT, Araújo RC, Mouro MG, Rosa TS, Higa EMS. Effects of training and nitric oxide on diabetic nephropathy progression in type I diabetic rats. Experimental Biology and Medicine (Maywood, N.J.) 2011;236(10):1180–7.
  39. Amaral LS de B, Souza CS, Volpini RA, Shimizu MHM, de Bragança AC, Canale D, et al. Previous Exercise Training Reduces Markers of Renal Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Female Rats. Journal of Diabetes Research 2018;2018:6170352.
  40. Amaral LS de B, Silva FA, Correia VB, Andrade CEF, Dutra BA, Oliveira MV, et al. Beneficial effects of previous exercise training on renal changes in streptozotocin-induced diabetic female rats. Experimental Biology and Medicine (Maywood, N.J.) 2016;241(4):437–45.
  41. Chen S, Hong SW, Iglesias-de la Cruz MC, Isono M, Casaretto A, Ziyadeh FN. The key role of the transforming growth factor-beta system in the pathogenesis of diabetic nephropathy. Renal Failure 2001;23(3–4):471–81.
  42. Kitamura M, Sütö TS. TGF-beta and glomerulonephritis: anti-inflammatory versus prosclerotic actions. Nephrology, Dialysis, Transplantation: Official Publication of the European Dialysis and Transplant Association - European Renal Association 1997;12(4):669–79.
  43. Wilson HM, Minto AWM, Brown PAJ, Erwig L-P, Rees AJ. Transforming growth factor-β isoforms and glomerular injury in nephrotoxic nephritis. Kidney International 2000;57(6):2434–44.
  44. Li JH, Huang XR, Zhu H-J, Johnson R, Lan HY. Role of TGF-β signaling in extracellular matrix production under high glucose conditions. Kidney International 2003;63(6):2010–9.
  45. Boor P, Celec P, Behuliak M, Grancic P, Kebis A, Kukan M, et al. Regular moderate exercise reduces advanced glycation and ameliorates early diabetic nephropathy in obese Zucker rats. Metabolism: Clinical and Experimental 2009;58(11):1669–77.
  46. Souza CS, de Sousa Oliveira BS, Viana GN, Correia TML, de Bragança AC, Canale D, et al. Preventive effect of exercise training on diabetic kidney disease in ovariectomized rats with type 1 diabetes. Experimental Biology and Medicine (Maywood, N.J.) 2019;244(9):758–69.
  47. Archer AE, Von Schulze AT, Geiger PC. Exercise, heat shock proteins and insulin resistance. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 2018;373(1738).
  48. Bellini S, Barutta F, Mastrocola R, Imperatore L, Bruno G, Gruden G. Heat Shock Proteins in Vascular Diabetic Complications: Review and Future Perspective. International Journal of Molecular Sciences 2017;18(12(.
  49. Chung J, Nguyen A-K, Henstridge DC, Holmes AG, Chan MHS, Mesa JL, et al. HSP72 protects against obesity-induced insulin resistance. Proceedings of the National Academy of Sciences 2008;105(5):1739–44.
  50. Yamagishi N, Nakayama K, Wakatsuki T, Hatayama T. Characteristic changes of stress protein expression in streptozotocin-induced diabetic rats. Life Sciences 2001;69(22):2603–9.
  51. Atalay M, Oksala NKJ, Laaksonen DE, Khanna S, Nakao C, Lappalainen J, et al. Exercise training modulates heat shock protein response in diabetic rats. Journal of Applied Physiology 2004;97(2):605–11.
  52. Lollo PCB, Moura CS, Morato PN, Amaya-Farfan J. Differential response of heat shock proteins to uphill and downhill exercise in heart, skeletal muscle, lung and kidney tissues. Journal of Sports Science & Medicine 2013;12(3):461–6.
  53. Fehrenbach E, Niess AM, Voelker K, Northoff H, Mooren FC. Exercise intensity and duration affect blood soluble HSP72. International Journal of Sports Medicine 2005;26(7):552–7.
  1. Peake JM, Suzuki K, Hordern M, Wilson G, Nosaka K, Coombes JS. Plasma cytokine changes in relation to exercise intensity and muscle damage. European Journal of Applied Physiology 2005;95(5–6):514–21.
Daneshvar Medicine
Volume 29, Issue 4 - Serial Number 155
November and December 2021
Pages 42-54