Document Type : Research Paper I Open Access I Released under CC BY-NC 4.0 license


1 PhD candidate of Exercise Physiology, Department of Physical Education and Sports Sciences, Najafabad Branch, Islamic Azad University, Najafabad, Iran

2 .Assistance Professor of Exercise Physiology, Department of Sports Sciences and Sport Medicine Research Center, Najafabad Branch, Islamic Azad University, Najafabad, Iran

3 Assistance Professor of Exercise Physiology, Department of Sport Sciences, Faculty of Humanities, Semnan University, Semnan, Iran

4 Assistance Professor of Exercise Physiology, Department of Sports Sciences and Sport Medicine Research Center, Najafabad Branch, Islamic Azad University, Najafabad, Iran


Improper regulation of mitochondrial dynamics is associated with dysregulation of metabolism and can lead to metabolic diseases. This study aimed to investigate the effect of aerobic training on gene expression of Drp1 and Cyp1a1 and protein expression of CYP1A1 in soleus muscle of male diabetic rats. In this experimental study, 24 male Wistar rats were randomly divided into 3 groups: diabetes (D), control (Ct), and exercise + diabetes (ED) group. The diabetic model was induced in rats by STZ injection. The ED group performed an aerobic training protocol five times a week for eight weeks. After the end of the protocol, rat soleus muscle was extracted, and gene expression of Drp1 and Cyp1a1 RT-PCR and protein expression of CYP1A1 were measured using ELIZA. RNA was calculated using the formula 2^(-ΔΔCT)and then the data were analyzed using ANOVA. The results showed a significant difference between groups in the gene expression of Drp1 (P0.001) and Cyp1a1 (P=0.017), protein expression of CYP1A1 (P=0.028), and glucose (P0.001). Diabetes increases the gene expression of Drp1 and Cyp1a1 and the protein expression of CYP1A1 in skeletal muscle. However, exercise could only reduce gene expression of Drp1 (P=0.013). Diabetes leads to increased glucose, gene expression of Drp1 and Cyp1a1, and protein expression of CYP1A1 in skeletal muscle. But the exercise could prevent only increase of gene expression of Drp1.However, exercise could only reduce Drp1 expression (P=0.013). Diabetes leads to increased glucose, gene expression of Drp1 and Cyp1a1, and protein expression of CYP1A1 in skeletal muscle.


Main Subjects

  1. Sobhani F, Haghshenas R, Rahimi M. Effect of eight weeks aerobic training and supplementation of green tea on apelin plasma levels and insulin resistance in elderly women with type 2 diabetes. Journal of Mazandaran University of Medical Sciences. 2019;28(170):84-93.
  2. Codella R, Terruzzi I, Luzi L. Why should people with type 1 diabetes exercise regularly? Acta diabetologica. 2017;54(7):615-30.
  3. Gilani N, Kazemnejad A, Zayeri F, Hadaegh F, Azizi F, Khalili D. Anthropometric indices as predictors of coronary heart disease risk: Joint modeling of longitudinal measurements and time to event. Iranian journal of public health. 2017;46(11):1546.
  4. Kirwan JP, Sacks J, Nieuwoudt S. The essential role of exercise in the management of type 2 diabetes. Cleveland Clinic journal of medicine. 2017;84(7 Suppl 1):S15.
  5. Hawley JA, Lessard S. Exercise training‐induced improvements in insulin action. Acta physiologica. 2008;192(1):127-35.
  6. Asmann YW, Stump CS, Short KR, Coenen-Schimke JM, Guo Z, Bigelow ML, et al. Skeletal muscle mitochondrial functions, mitochondrial DNA copy numbers, and gene transcript profiles in type 2 diabetic and nondiabetic subjects at equal levels of low or high insulin and euglycemia. Diabetes. 2006;55(12):3309-19.
  7. Garber CE, Blissmer B, Deschenes MR, Franklin BA, Lamonte MJ, Lee I-M, et al. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Medicine and science in sports and exercise. 2011;43(7):1334-59.
  8. Smirnova E, Griparic L, Shurland D-L, Van Der Bliek AM. Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Molecular biology of the cell. 2001;12(8):2245-56.
  9. Mears JA, Lackner LL, Fang S, Ingerman E, Nunnari J, Hinshaw JE. Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission. Nature structural & molecular biology. 2011;18(1):20.
  10. Guo J, Ye F, Jiang X, Guo H, Xie W, Zhang Y, et al. Drp1 mediates high glucose-induced mitochondrial dysfunction and epithelial-mesenchymal transition in endometrial cancer cells. Experimental cell research. 2020;389(1):111880.
  11. Gusdon AM, Callio J, Distefano G, O'Doherty RM, Goodpaster BH, Coen PM, et al. Exercise increases mitochondrial complex I activity and DRP1 expression in the brains of aged mice. Experimental gerontology. 2017;90:1-13.
  12. Moore TM, Zhou Z, Cohn W, Norheim F, Lin AJ, Kalajian N, et al. The impact of exercise on mitochondrial dynamics and the role of Drp1 in exercise performance and training adaptations in skeletal muscle. Molecular metabolism. 2019;21:51-67.
  13. Wang XL, Greco M, Sim AS, Duarte N, Wang J, Wilcken DE. Effect of CYP1A1 MspI polymorphism on cigarette smoking related coronary artery disease and diabetes. Atherosclerosis. 2002;162(2):391-7.
  14. Omura T. Forty years of cytochrome P450. Biochemical and biophysical research communications. 1999;266(3):690-8.
  15. Hasler JA, Estabrook R, Murray M, Pikuleva I, Waterman M, Capdevila J, et al. Human cytochromes P450. Molecular aspects of medicine. 1999;20(1-2):1-137.
  16. Manikandan P, Nagini S. Cytochrome P450 structure, function and clinical significance: a review. Current drug targets. 2018;19(1):38-54.
  17. Knudsen JG, Bertholdt L, Gudiksen A, Gerbal-Chaloin S, Rasmussen MK. Skeletal muscle interleukin-6 regulates hepatic cytochrome P450 expression: effects of 16-week high-fat diet and exercise. Toxicological Sciences. 2018;162(1):309-17.
  18. Ardies CM, Zachman EK, Koehn BJ. Effect of swimming exercise and ethanol on rat liver P450-dependent monooxygenases. Medicine and science in sports and exercise. 1994;26(12):1453-8.
  19. Gollasch B, Dogan I, Rothe M, Gollasch M, Luft FC. Maximal exercise and plasma cytochrome P450 and lipoxygenase mediators: A lipidomics study. Physiological reports. 2019;7(13):e14165.
  20. Furman BL. Streptozotocin‐induced diabetic models in mice and rats. Current protocols in pharmacology. 2015;70(1):5.47. 1-5.. 20.
  21. Haghshenas R, Jafari M, Ravasi A, Kordi M, Gilani N, Shariatzadeh M, et al. The effect of eight weeks endurance training and high-fat diet on appetite-regulating hormones in rat plasma. Iranian journal of basic medical sciences. 2014;17(4):237.
  22. Haghshenas R, Gilani N, Jafari M. Effect of 16 weeks endurance training and high fat diet on plasma level of interleukins-6, 10 and nesfatin-1 of rats. Sport Physiol. 2015;6(24):49-61.
  23. Tanaka T, Nishimura A, Nishiyama K, Goto T, Numaga-Tomita T, Nishida M. Mitochondrial dynamics in exercise physiology. Pflügers Archiv-European Journal of Physiology. 2020;472(2):137-53.
  24. Peyravi A, Yazdanpanahi N, Nayeri H, Hosseini SA. The effect of endurance training with crocin consumption on the levels of MFN2 and DRP1 gene expression and glucose and insulin indices in the muscle tissue of diabetic rats. Journal of food biochemistry. 2020;44(2):e13125.
  25. Fealy CE, Mulya A, Lai N, Kirwan JP. Exercise training decreases activation of the mitochondrial fission protein dynamin-related protein-1 in insulin-resistant human skeletal muscle. Journal of Applied Physiology. 2014;117(3):239-45.
  26. Züchner S, Mersiyanova IV, Muglia M, Bissar-Tadmouri N, Rochelle J, Dadali EL, et al. Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nature genetics. 2004;36(5):449-51.
  27. Bach D, Naon D, Pich S, Soriano FX, Vega N, Rieusset J, et al. Expression of Mfn2, the Charcot-Marie-Tooth neuropathy type 2A gene, in human skeletal muscle: effects of type 2 diabetes, obesity, weight loss, and the regulatory role of tumor necrosis factor α and interleukin-6. Diabetes. 2005;54(9):2685-93.
  28. Androutsopoulos VP, Tsatsakis AM, Spandidos DA. Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention. BMC cancer. 2009;9(1):1-17.
  29. Chatuphonprasert W, Nemoto N, Sakuma T, Jarukamjorn K. Modulations of cytochrome P450 expression in diabetic mice by berberine. Chemico-biological interactions. 2012;196(1-2):23-9.
  30. Su Y-H, Yuan Q-K, Xiao R, Chen J, Li Q, Zhang S-C. Effects of resistance training on mitochondrial function in skeletal muscle of aging rats. Chinese Journal of Applied Physiology. 2020;36(2):165.