Comparing the Effect of Continuous and Intermittent Exercise Training Regimens on soleus GLUT4, AMPK and Insulin Receptor in Streptozotocin-Induced Diabetic Rats

Document Type: Original Article

Authors

1 Assistant Professor, Department of Sport Sciences, Ilam Branch, Islamic Azad University, Ilam, Iran

2 Assistant Professor, Department of Sport Sciences, University of Bojnord, Bojnord, Iran

Abstract

Background: The impact of continuous and intermittent training on diabetes mellitus condition and its mechanism is not well understood. The aim of the present study was to assess the changes in glucose uptake after 6 weeks of continuous and intermittent exercise training protocols in healthy and streptozotocin (STZ)-induced diabetic rats.
Method: Sixty male albino Wistar rats (13 weeks old) were randomly divided into six groups including healthy control, healthy continuous, healthy intermittent, diabetic control, diabetic continuous, and diabetic intermittent groups. Animals ran continuously and intermittently on treadmill for 6 weeks. They got diabetes using STZ (50 mg per kg of body weight).
Results: STZ increased blood glucose levels and insulin resistance in diabetic rats. In contrast, STZ reduced insulin, insulin receptor (IR), glucose transporter type 4 (GLUT4), and 5' adenosine monophosphate-activated protein kinase (AMPK) levels in diabetic rats. However, both continuous and intermittent exercise training protocols improved insulin resistance and prevented the reduction of GLUT4 and AMPK in diabetic rats. Neither of continuous and intermittent exercise trainings had any effect on insulin and IR receptor.
Conclusions: Continuous and intermittent exercise trainings comparably reduce blood glucose and subsequently improve insulin resistance by increasing GLUT4 and AMPK independent of insulin and its receptors.

Keywords


  1. Abou-Seif MA, Youssef AA. Evaluation of some biochemical changes in diabetic patients. Clin Chim Acta 2004; 346(2):161-70.
  2. Gomez-Perez FJ, Aguilar-Salinas CA, Almeda-Valdes P, Cuevas-Ramos D, Garber IL, Rull JA. HbA1c for the diagnosis of diabetes mellitus in a developing country. a position article. Arch Med Res 2010; 41(4):302-8.
  3. Cao S, Li B, Yi X, Chang B, Zhu B, Lian Z, et al. Effects of exercise on AMPK signaling and downstream components to PI3K in rat with type 2 diabetes. PLoS One 2012; 7(12):e51709.
  4. McGee SL, Howlett KF, Starkie RL, Cameron-Smith D, Kemp BE, Hargreaves M. Exercise increases nuclear AMPK alpha2 in human skeletal muscle. Diabetes 2003; 52(4):926-8.
  5. Park ST, Kim K, Yoon JH, Lee S. Effect of exercise on GLUT4 expression of skeletal muscle in streptozotocin-induced diabetic rats. Journal of Exercise Physiology Online 2011; 14(3):113-22.
  6. Kim Y, Park CW. Adenosine monophosphate–activated protein kinase in diabetic nephropathy. Kidney Res Clin Pract 2016; 35(2):69-77.
  7. Coughlan KA, Valentine RJ, Ruderman, NB, Saha AK. AMPK activation: a therapeutic target for type 2 diabetes? Diabetes Metab Syndr Obes 2014; 7:241-53.
  8. Habegger KM, Hoffman NJ, Ridenour CM, Brozinick JT, Elmendorf JS. AMPK enhances insulin-stimulated GLUT4 regulation via lowering membrane cholesterol. Endocrinology 2012; 153(5):2130-41.
  9. Chou CH, Tsai YL, Hou CW, Lee HH, Chang WH, Lin TW, et al. Glycogen overload by postexercise insulin administration abolished the exercise-induced increase in GLUT4 protein. J Biomed Sci 2005; 12(6):991-8.
  10. Tsai YL, Hou CW, Liao YH, Chen CY, Lin FC, Lee WC, et al. Exercise training exacerbates tourniquet ischemia-induced decreases in GLUT4 expression and muscle atrophy in rats. Life Sci 2006; 78(25):2953-9.
  11. Holten MK, Zacho M, Gaster M, Juel C, Wojtaszewski JF, Dela F. Strength training increases insulin-mediated glucose uptake, GLUT4 content, and insulin signaling in skeletal muscle in patients with type 2 diabetes. Diabetes 2004; 53(2):294-305.
  12. Christ CY, Hunt D, Hancock J, Garcia-Macedo R, Mandarino LJ, Ivy JL. Exercise training improves muscle insulin resistance but not insulin receptor signaling in obese zucker rats. J Appl Physiol 2002; 92(2):736-44.
  13. Slentz CA, Gulve EA, Rodnick KJ, Henriksen EJ, Youn JH, Holloszy JO. Glucose transporters and maximal transport are increased in endurance-trained rat soleus. J Appl Physiol (1985) 1992; 73(2):486-92.
  14. Lehnen AM, Angelis KD, Markoski MM, Schaan BD. Changes in the GLUT4 Expression by acute exercise, Exercise training and detraining in experimental models. J Diabetes Metab 2012; 10:2-8.
  15. Ivy JL. Muscle insulin resistance amended with exercise training: role of GLUT4 expression. Med Sci Sports Exerc 2004; 36(7):1207-11.
  16. Mackenzie R, Maxwell N, Castle P, Elliott B, Brickley G, Watt P. Intermittent exercise with and without hypoxia improves insulin sensitivity in individuals with type 2 diabetes. J Clin Endocrinol Metab 2012; 97(4):E546-55.
  17. Essen B, Hagenfeldt L, Kaijser L. Utilization of blood‐borne and intramuscular substrates during continuous and intermittent exercise in man. J Physiol 1977; 265(2):489-506.
  18. Yousefi MR, Taheri Chadorneshin H. The effect of moderate endurance training on gastrocnemius retinol-binding protein 4 and insulin resistance in streptozotocin-induced diabetic rats. Interv Med Appl Sci 2018; 10(1):59-63.
  19. Kim JS, Lee YH, Kim JC, Ko YH, Yoon CS, Yi HK. Effect of exercise training of different intensities on anti-inflammatory reaction in streptozotocin-induced diabetic rats. Biol Sport 2014; 31(1):73-9.
  20. Molanouri Shamsi M, Hassan ZH, Gharakhanlou R, Quinn LS, Azadmanesh K, Baghersad L, et al. Expression of interleukin-15 and inflammatory cytokines in skeletal muscles of STZ-induced diabetic rats: effect of resistance exercise training. Endocrine 2014; 46(1):60-9.
  21. Strotmeyer ES, De Rekeneire N, Schwartz AV, Resnick HE, Goodpaster BH, Faulkner KA, et al. Sensory and motor peripheral nerve function and lower-extremity quadriceps strength: The health, aging and body composition study. J Am Geriatr Soc 2009; 57(11):2004-10.
  22. Chiles NS, Phillips CL, Volpato S, Bandinelli S, Ferrucci L, Guralnik JM, et al. Diabetes, peripheral neuropathy, and lower-extremity function. J Diabetes Complications 2014; 28(1):91-5.
  23. Lee JS, Auyeung TW, Leung J, Kwok T, Leung PC, Woo J. The effect of diabetes mellitus on age‐associated lean mass loss in 3153 older adults. Diabet Med 2010; 27(12):1366-71.
  24. Thomson D. The role of AMPK in the regulation of skeletal muscle size, hypertrophy, and regeneration. Int J Mol Sci 2018; 19(10):E3125.
  25. Frøsig C, Rose AJ, Treebak JT, Kiens B, Richter EA, Wojtaszewski JF. Effects of endurance exercise training on insulin signaling in human skeletal muscle. Diabetes 2007; 56(8):2093-102.
  26. Chakaroun R, Raschpichler M, Klöting N, Oberbach A, Flehmig G, Kern M, et al. Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity. Metabolism 2012; 61(5):706-14.
  27. Gavin C, Sigal RJ, Cousins M, Menard ML, Atkinson M, Khandwala F, et al. Resistance exercise but not aerobic exercise lowers remnant-like lipoprotein particle cholesterol in type 2 diabetes: a randomized controlled trial. Atherosclerosis 2010; 213(2):552-7.
  28. Bird SR, Hawley JA. Exercise and type 2 diabetes: new prescription for an old problem. Maturitas 2012; 72(4):311-6.
  29. Ploug T, Van Deurs B, Ai H, Cushman SW, Ralston E. Analysis of GLUT4 distribution in whole skeletal muscle fibers: identification of distinct storage compartments that are recruited by insulin and muscle contractions. J Cell Biol 1998; 142(6):1429-46.
  30. Luciano E, Carneiro EM, Carvalho CR, Carvalheira JB, Peres SB, Reis MA, et al. Endurance training improves responsiveness to insulin and modulates insulin signal transduction through the phosphatidylinositol 3-kinase/Akt-1 pathway. Eur J Endocrinol 2002; 147(1):149-57.
  31. Chibalin AV, Yu M, Ryder JW, Song XM, Galuska D, Krook A, et al. Exercise-induced changes in expression and activity of proteins involved in insulin signal transduction in skeletal muscle: differential effects on insulin-receptor substrates 1 and 2. Proc Natl Acad Sci U S A 2000; 97(1):38-43.
  32. Neufer PD, Shinebarger MH, Dohm GL. Effect of training and detraining on skeletal muscle glucose transporter (GLUT4) content in rats. Can J Physiol Pharmacol 1992; 70(9):1286-90.
  33. Rose AJ, Jeppesen J, Kiens B, Richter EA. Effects of contraction on localization of GLUT4 and v-SNARE isoforms in rat skeletal muscle. Am J Physiol Regul Integr Comp Physiol 2009; 297(5):R1228-37.
  34. Yu ZW, Burén J, Enerbäck S, Nilsson E, Samuelsson L, Eriksson JW. Insulin can enhance GLUT4 gene expression in 3T3-F442A cells and this effect is mimicked by vanadate but counteracted by cAMP and high glucose–potential implications for insulin resistance. Biochim Biophys Acta 2001; 1535(2):174-85.
  35. Holmes B, Dohm GL. Regulation of GLUT4 gene expression during exercise. Med Sci Sports Exerc 2004; 36(7):1202-6.
  36. Richter EA, Hargreaves M. Exercise, GLUT4, and skeletal muscle glucose uptake. Physiol Rev 2013; 93(3):993-1017.
  37. Holloszy JO. Regulation of mitochondrial biogenesis and GLUT4 expression by exercise. Compr Physiol 2011; 1(2):921-40.
  38. Musi N, Fujii N, Hirshman MF, Ekberg I, Fröberg S, Ljungqvist O, et al. AMP-activated protein kinase (AMPK) is activated in muscle of subjects with type 2 diabetes during exercise. Diabetes 2001; 50(5):921-27.
  39. Nielsen JN, Mustard KJ, Graham DA, Yu H, MacDonald CS, Pilegaard H, et al. 5'AMP-activated protein kinase activity and subunit expression in exercise-trained human skeletal muscle. J Appl Physiol (1985) 2003; 94(2):631-41.
  40. Frosig C, Jorgensen SB, Hardie DG, Richter EA, Wojtaszewski JF. 5'-AMP-activated protein kinase activity and protein expression are regulated by endurance training in human skeletal muscle. Am J Physiol Endocrinol Metab 2004; 286(3):E411-7.
  41. McConell GK, Lee‐Young RS, Chen ZP, Stepto NK, Huynh NN, Stephens TJ, et al. Short‐term exercise training in humans reduces AMPK signalling during prolonged exercise independent of muscle glycogen. J Physiol 2005; 568(2):665-76.
  42. Clark SA, Chen ZP, Murphy KT, Aughey RJ, McKenna MJ, Kemp BE, et al. Intensified exercise training does not alter AMPK signalling in human skeletal muscle. Am J Physiol Endocrinol Metab 2004; 286(5):E737-43.
  43. Kuhl JE, Ruderman NB, Musi N, Goodyear LJ, Patti ME, Crunkhorn S, et al. Exercise training decreases the concentration of malonyl CoA and increases the expression and activity of malonyl CoA decarboxylase in human muscle. Am J Physiol Endocrinol Metab 2006; 290(6):E1296-303.
  44. Misra P, Chakrabarti R. The role of AMP kinase in diabetes. Indian J Med Res 2007; 125(3):389-98.