The effect of aerobic training on insulin resistance and AMPK/PI3K axis in Soleus muscle of type 2 diabetic rats

Document Type : Research Paper

Authors

1 Ph.D student, Department of Exercise physiology, Borujerd Branch, Islamic Azad University, Borujerd, Iran

2 Department of Exercise Physiology, Saveh Branch, Islamic Azad University, Saveh, Iran.

3 Department of Exercise physiology, Borujerd Branch, Islamic Azad University, Borujerd, Iran

Abstract

Introduction: The role of genetic components in hypertrophy and glycemic profile especially in the presence of type 2 diabetes is well defined. This study aimed to determine the effect of aerobic training on AMPK/PI3K axis in Soleus muscle and insulin resistance in type 2 diabetic rats.
Methods: For this purpose, type 2 diabetic induced in fourteen male Wistar rats aged 10 week (220 ± 10 g) by intraperitoneal injection of nicotinamide and STZ and were randomly selected in exercise (n = 7) and control (n = 7) groups. The exercise rats participated in an aerobic training program (5 times weekly) in the form of running on the treadmill. 48 hours after the lasting exercise session, PI3K and AMPK expression in soleus muscle as well as fasting glucose were measured. Fasting glucose and insulin values were used to calculate insulin resistance. Data compared by independent t test between groups.
Results: Compared to control group, aerobic training resulted in significant increase in PI3K expression in soleus muscle (P = 0.005) and significant decrease in fasting glucose (P = 0.001) and insulin resistance (P = 0.010). AMPK expression did not change in response to aerobic training compare with control group (P = 0.238).
Conclusion: Based on these data, improved glucose and insulin resistance in response to aerobic training may be attributed to increased PI3K expression in soleus muscle. Understanding the mechanisms responsible for hypertrophy in response to exercise requires more studies in this area.

Keywords

Main Subjects

References

  1. Al-Dwairi A, Alfaqih MA, Saadeh RA, Al-Shboul O, Alqudah M, Khanfar M, Khassawneh A. Lack of glycemic control in type two diabetes mellitus patients is associated with reduced serum epidermal growth factor level and increased insulin resistance. Biomed Rep. 2024 Oct 29; 22(1):5.
  2. Wang H, Shan C, Guo G, Ning D, Miao F. Therapeutic potential of palmitoleic acid in non-alcoholic fatty liver disease: Targeting ferroptosis and lipid metabolism disorders. Int Immunopharmacol. 2024 Dec 5; 142(Pt A):113025.
  1. Amra C. The T-Allele of TCF7L2 rs7903146 Associates with a Reduced Compensation of Insulin Secretion for Insulin Resistance Induced by 9 Days of Bed Rest. DIABETES 2010; 59: 836-43.
  2. Göransson O, McBride A, Hawley SA, Ross FA, Shpiro N, Foretz M, et al. Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase. J Biol Chem 2007; 282(45): 32549-60.
  3. Chen L, Jiao ZH, Zheng LS, Zhang YY, Xie ST, Wang ZX, et al. Structural insight into the autoinhibition mechanism of AMP-activated protein kinase. Nature 2009; 459(7250): 1146-9.
  4. Ross FA, Jensen TE, Hardie DG. Differential regulation by AMP and ADP of AMPK complexes containing different γ subunit isoforms. Biochem J. 2016; 473:189–199.
  1. Garcia D, Shaw RJ. AMPK: Mechanisms of Cellular Energy Sensing and Restoration of Metabolic Balance. Mol Cell. 2017; 66:789–800.
  2. Huang X, Liu G, Guo J, Su Z. The PI3K/AKT pathway in obesity and type 2 diabetes. Int J Biol Sci. 2018 Aug 6; 14(11):1483-1496.
  1. James SR, Downes CP, Gigg R, Grove SJ, Holmes AB, Alessi DR. Specific binding of the Akt-1 protein kinase to phosphatidylinositol 3,4,5-trisphosphate without subsequent activation. Biochem J. 1996 May 1; 315:709-13.
  2. Sussman MA, Völkers M, Fischer K, Bailey B, Cottage CT, Din S, et al. Myocardial AKT: the omnipresent nexus. Physiol Rev. 2011 Jul; 91(3):1023-70.
  3. Jiang ZY, Lin YW, Clemont A, Feener EP, Hein KD, Igarashi M, Yamauchi T, White MF, King GL. Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats. J Clin Investig. 1999; 104(4):447–57.
  1. De Nigris V, Pujadas G, La Sala L, Testa R, Genovese S, Ceriello A. Shortterm high glucose exposure impairs insulin signaling in endothelial cells. Cardiovas Diabetol. 2015; 14:114.
  1. Ji Hee Lee, Jae Eun Park, Ji Sook Han. Fucoidan Stimulates Glucose Uptake via the PI3K/AMPK Pathway and Increases Insulin Sensitivity in 3T3-L1 Adipocytes. Journal of Life Science. 2021; 31(1): 1-9.
  1. Vieira RFL, Junqueira RL, Gaspar RC, Muñoz VR, Pauli JR. Exercise activates AMPK signaling: impact on glucose uptake in the skeletal muscle in aging. J Rehab Therapy.2020; 2(2):48-53.
  2. Tao R, Gong J, Luo X, Zang M, Guo W, Wen R, Luo Z. AMPK exerts dual regulatory effects on the PI3K pathway. J Mol Signal. 2010 Feb 18; 5(1):1. doi: 10.1186/1750-2187-5-1.
  3. Kate L. Weeks and Julie R. McMullen. The Athlete's Heart vs. the Failing Heart: Can Signaling Explain the Two Distinct Outcomes? Physiology. 2011; 26(2):97-105.
  4. 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.
  5. 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.
  6. Eizadi M, Soory R, Ravasi A, Baesy K, Choobineh S. Relationship between TCF7L2 Relative Expression in Pancreas Tissue with Changes in Insulin by High Intensity Interval Training (HIIT) in Type 2 Diabetes Rats . JSSU. 2017; 24 (12):981-993.
  7. Ghahramani M, Banaei Far, Arshadi, Sohaily. Effect of aerobic training on expression of PGC-1A&PEPCK genes in hepatocyte of streptozotocin induced diabetic mare rats. Stud Med Sci. 2019; 30 (10):791-802.
  8. McAuley KA, Williams SM, Mann JI, Walker RJ, Lewis-Barned NJ, Temple LA, Duncan AW. Diagnosing insulin resistance in the general population. Diabetes Care. 2001 Mar; 24(3):460-4.
  9. Maltais ML, Perreault K, Courchesne-Loyer A, Lagacé JC, Barsalani R, Dionne IJ. Effect of Resistance Training and Various Sources of Protein Supplementation on Body Fat Mass and Metabolic Profile in Sarcopenic Overweight Older Adult Men: A Pilot Study. Int J Sport Nutr Exerc Metab. 2016 Feb; 26(1):71-7.
  10. Vancea DM, Vancea JN, Pires MI, Reis MA, Moura RB, Dib SA. Effect of frequency of physical exercise on glycemic control and body composition in type 2 diabetic patients. Arq Bras Cardiol. 2009; 92(1):23-30.
  11. Leggate M, Carter WG, Evans MJ, Vennard RA, Sribala-Sundaram S, MA. Determination J Appl Physiol (1985). 2012 Apr; 112(8):1353-60.
  12. Glans F, Eriksson KF, Segerström A, Thorsson O, Wollmer P, Groop L. Evaluation of the effects of exercise on insulin sensitivity in Arabian and Swedish women with type 2 diabetes. Diabetes Res Clin Pract. 2009 Jul; 85(1):69-74.
  13. Lopes WA, Leite N, da Silva LR, Brunelli DT, Gáspari AF, Radominski RB, et al. Effects of 12 weeks of combined training without caloric restriction on inflammatory markers in overweight girls. J Sports Sci. 2016 Oct; 34(20):1902-12.
  1. Deshmukh A, Coffey VG, Zhong Z, Chibalin AV, Hawley JA, Zierath JR. Exercise-induced phosphorylation of the novel Akt substrates AS160 and filamin A in human skeletal muscle. Diabetes. 2006; 55(6): 1776–1782.
  2. Wojtaszewski JFP, Hansen BF, Gade J. Insulin signaling and insulin sensitivity after exercise in human skeletal muscle. Diabetes. 2000; 49(3): 325–331.
  3. Cusi K, Maezono A. Osman. Insulin resistance differentially affects the PI 3-kinase- andMAP kinase-mediated signaling in human muscle. The Journal of Clinical Investigation. 2000; 105(3). 311–320.
  4. Howlett KF, Sakamoto K, Yu H, Goodyear LJ, Hargreaves M. Insulin-stimulated insulin receptor substrate-2- associated phosphatidylinositol 3-kinase activity is enhanced in human skeletal muscle after exercise, Metabolism: Clinical and Experimental. 2000; 55(8): 1046–1052.
  5. Ma Z, Qi J, Meng S, Wen B, Zhang J. Swimming exercise training-induced left ventricular hypertrophy involves microRNAs and synergistic regulation of the PI3K/AKT/mTOR signaling pathway. Eur J Appl Physiol. 2013 Oct; 113(10):2473-86.
  1. Perrino C, Schroder JN, Lima B. Dynamic regulation of phosphoinositide 3-kinase-gamma activity and beta-adrenergic receptor trafficking in end-stage human heart failure. Circulation. 2007; 116(22):2571–2579.
  1. 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.
  1. Takekoshi K, Fukuhara M, Quin Z, Nissato S, Isobe K, Kawakami Y, et al. Long-term exercise stimulates adenosine monophosphate–activated protein kinase activity and subunit expression in rat visceral adipose tissue and liver. Metabolism. 2006; 55(8):1122-8.
  2. 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.
  3. Zachwieja JJ, Toffolo G, Cobelli C, Bier DM, Yarasheski KE. Resistance exercise and growth hormone administration in older men: effects on insulin sensitivity and secretion during a stable-label intravenous glucose tolerance test. Metabolism. 1996 Feb; 45(2):254-60.
Medical Journal of Mashhad university of Medical Sciences
Volume 68, Issue 1
March and April 2025
Pages 32-40

Files

Share

How to cite

Statistics