The effect of endurance training on expression of AMPK and AKT in liver tissue of diabetics male rats.

Document Type : Original Article

Authors

1 , Department of Sport Sciences, Faculty of Humanities, Semnan University, Semnan, Iran.

2 Department of Sport Sciences, Faculty of Humanities, Semnan University, Semnan, Iran.

Abstract

Abstract

The aim of this study was to investigated the effect of endurance training on the gene and protein expression of adenosine monophosphate-activated protein kinase (AMPK) and protein kinase B (AKT) in liver tissue of male rats with diabetes. In this experimental study, 32 male Wistar rats were randomly divided to 4 groups: diabetic group (D), control group (C), exercise group (E), Exercise and diabetic group (ED). Then 16 rats received Strepotozocin injection to induce diabetes. Groups of E and ED performed the designed aerobic exercise protocol five sessions per week for eight weeks. At the end of the protocol, rat liver tissue was extracted, RT-PCR was used to measure gene expression and Western blot and immunohistochemistry were used to express AMPK and AKT proteins, respectively. Then RNA was calculated using the formula of 2-DDCT and the data of gene and protein expression AMPK were analyzed with univariate analysis of variance. The results showed that there was no significant difference between AMPK and AKT between group E and group C in both RNA and protein levels (P>0.05). In group D compared to group C in the level of protein, both variables were significantly reduced (P<0.001), AKT was significantly decreased at RNA level (P<0.033) and AMPK was significantly increased (P<0.001). Both variables in protein level were significantly increased in group ED compared to group D (P<0.001), while changes in RNA level were not significant. Diabetes exerts destructive effects on liver tissue by reducing AMPK and AKT and disrupting pathways dependent on these variables, and aerobic exercise can improve diabetes by increasing these two variables to some extent.

Keywords


  1. Moscatiello S, Manini R, Marchesini G. Diabetes and liver disease: an ominous association. Nutrition, Metabolism and Cardiovascular Diseases. 2007;17(1):63-70.
  2. Chiang DJ, Pritchard MT, Nagy LE. Obesity, diabetes mellitus, and liver fibrosis. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2011;300(5):G697-G702.
  3. Umezawa S, Higurashi T, Nakajima A. AMPK: therapeutic target for diabetes and cancer prevention. Current pharmaceutical design. 2017;23(25):3629-44.
  4. Garcia D, Mihaylova MM, Shaw RJ. AMPK: Central Regulator of Glucose and Lipid Metabolism and Target of Type 2 Diabetes Therapeutics. The Liver: Biology and Pathobiology. 2020:472-84.
  5. Oakhill JS, Scott JW, Kemp BE. AMPK functions as an adenylate charge-regulated protein kinase. Trends in Endocrinology & Metabolism. 2012;23(3):125-32.
  6. Foretz M, Ancellin N, Andreelli F, Saintillan Y, Grondin P, Kahn A, et al. Short-term overexpression of a constitutively active form of AMP-activated protein kinase in the liver leads to mild hypoglycemia and fatty liver. Diabetes. 2005;54(5):1331-9.
  7. Banerjee RR, Rangwala SM, Shapiro JS, Rich AS, Rhoades B, Qi Y, et al. Regulation of fasted blood glucose by resistin. Science. 2004;303(5661):1195-8.
  8. Liu Y, Deng J, Fan D. Ginsenoside Rk3 ameliorates high-fat-diet/streptozocin induced type 2 diabetes mellitus in mice via the AMPK/Akt signaling pathway. Food & function. 2019;10(5):2538-51.
  9. Li Y, Huang D, Zheng L, Cao H, Fan Z. Effect of microRNA‐141 on the development of diabetic nephropathy through regulating AKT/AMPK signaling pathway by targeting insulin receptor substrate 2. Journal of cellular biochemistry. 2019;120(5):8008-15.
  10. O'neill HM. AMPK and exercise: glucose uptake and insulin sensitivity. Diabetes & metabolism journal. 2013;37(1):1.
  11. Maghami M, Keshavarz S, Haghshenas R, Eftekhari E. The Effect of Endurance Training and Nettle Consumption on Protein and Gene Expression of AKT and GLUT4 in Soleus Muscle of Diabetic Male Rats. Iranian Journal of Diabetes and Metabolism. 2021;21(4):240-9.
  12. 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.
  13. Haghshenas R, Ravasi A, Kordi M, Hedayati M, Shabkhiz F, Shariatzade Joneidi M. Effects of twelve weeks endurance training on weight, food intake, and plasma levels of nesfatin-1 in obese male rats. J Sport Biomotor Sci. 2012;5(1):77-85.
  14. Nori P, Haghshenas R. Effects of eight weeks aerobic training on kynurenine and gene and protein expression of aryl hydrocarbon receptor in the heart of male rats. Koomesh. 2022;24(1):162-7.
  15. Hagh Shenas 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 Physiology. 2015;6(24):49-60.
  16. Haghshenas R, Ravasi AA, Kordi MR, Hedayati M, Shabkhiz F, Shariatzadeh M. The effect of a 12-week endurance training on IL-6, IL-10 and Nesfatin-1 plasma level of obese male rats. Journal of Sport Biosciences. 2013;5(4):109-22.
  17. Liu Y, Deng J, Fan DJF, function. Ginsenoside Rk3 ameliorates high-fat-diet/streptozocin induced type 2 diabetes mellitus in mice via the AMPK/Akt signaling pathway. 2019;10(5):2538-51.
  18. Zheng T, Yang X, Wu D, Xing S, Bian F, Li W, et al. Salidroside ameliorates insulin resistance through activation of a mitochondria‐associated AMPK/PI3K/A kt/GSK 3β pathway. British journal of pharmacology. 2015;172(13):3284-301.
  19. Friedrichsen M, Mortensen B, Pehmøller C, Birk JB, Wojtaszewski JF. Exercise-induced AMPK activity in skeletal muscle: role in glucose uptake and insulin sensitivity. Molecular and cellular endocrinology. 2013;366(2):204-14.
  20. Ruderman N, Park H, Kaushik V, Dean D, Constant S, Prentki M, et al. AMPK as a metabolic switch in rat muscle, liver and adipose tissue after exercise. Acta physiologica Scandinavica. 2003;178(4):435-42.
  21. Nazari GT, Ebrahimi M, Haghshenas R, Saeidi ZT. The effect of 12-week yoga selected exercise on fasting glucose, glycosylated hemoglobin and lipid profile in patients with type 2 diabetes. 2014.
  22. 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.
  23. Maghami M, Keshavarz S, Haghshenas R, Eftekhari E. Effect of aerobic exercise on gene expression of Drp1 and Cyp1a1 and protein expression of CYP1A1 in the soleus muscle of male diabetic rats. Journal of Sport Biosciences. 2021;13(3):301-12.
  24. Sriwijitkamol A, Coletta DK, Wajcberg E, Balbontin GB, Reyna SM, Barrientes J, et al. Effect of acute exercise on AMPK signaling in skeletal muscle of subjects with type 2 diabetes: a time-course and dose-response study. Diabetes. 2007;56(3):836-48.
  25. Ko JR, Seo DY, Kim TN, Park SH, Kwak H-B, Ko KS, et al. Aerobic exercise training decreases hepatic asprosin in diabetic rats. Journal of clinical medicine. 2019;8(5):666.
  26. Lee H, Zandkarimi F, Zhang Y, Meena JK, Kim J, Zhuang L, et al. Energy-stress-mediated AMPK activation inhibits ferroptosis. Nature cell biology. 2020;22(2):225-34.
  27. Horii N, Hasegawa N, Fujie S, Uchida M, Iemitsu K, Inoue K, et al. Effect of combination of chlorella intake and aerobic exercise training on glycemic control in type 2 diabetic rats. Nutrition. 2019;63:45-50.