Effects of prolonged whey protein supplementation and resistance training on the gene expression of IGF-1 and gastrocnemius muscle weight in young male Wistar rats

Document Type : Original Article


Department of Exercise Physiology, Faculty of Sport Sciences, Shahid Rajaee Teacher Training University, Tehran, Iran


This study aimed to investigate the combined effect of prolonged whey protein supplementation and resistance training on the expression of insulin-like growth factor-1 (IGF-1) gene, the weight of the Gastrocnemius muscle and One-repetition maximum in young male Wistar rats. In this study, twenty-one young male Wistar rats, aged eight weeks and weighing between 200 to 250 grams, were randomly assigned to four groups: training (T), supplementary training (ST), Sham (Sh), and control (C). The resistance training program was conducted for six weeks, five days a week, with the training intensity increasing from 50 to 100% of the rats' body weight. The rats receiving the whey supplement via the gavage method based on their body weight, using whey production by ON company. Forty-eight hours after the final training session, the quadriceps muscles of the rats were extracted and the expression level of the IGF-1 gene was evaluated using the Real-Time PCR method. Statistical analysis was conducted using one-way variance test and Scheffe's test. The results showed that the training -supplement group exhibited a significant increase in IGF-1 expression compared to the Sham group (P˂0.05). Moreover, the weight of the Gastrocnemius muscle of rats and also One-repetition maximum in the training-supplement group significantly increased compared to the training, sham, and control groups (P˂0.05). The findings suggest that the concomitant use of resistance training and whey protein supplementation has a synergistic effect on IGF-1 gene expression in skeletal muscle, which may contribute to enhanced muscle hypertrophy and One-repetition maximum.

What is already known on this subject?

Some of the main points from this article include:

  • Resistance training can stimulate GH secretion, which in turn increases IGF-1 production.
  • Whey protein supplementation can provide essential amino acids that are necessary for IGF-1 synthesis and activation.
  • Resistance training and whey protein supplementation can activate the PI3K/Akt/mTOR pathway, which is a signaling cascade that mediates the anabolic effects of IGF-1 on muscle protein synthesis and hypertrophy.
  • The effects of resistance training and whey protein supplementation on IGF-1 regulation may be influenced by various factors, such as age, sex, and training status.
  • Resistance training and whey protein supplementation can have positive effects on muscle growth and size by impacting the metabolic regulation of IGF-1. 


What this study adds?

The present study was the first research that investigated the combined effect of prolonged whey protein supplementation and resistance training on the expression of insulin-like growth factor-1 (IGF-1) gene and the weight of the Gastrocnemius muscle in young male Wistar rats. In addition, the results showed that the selected interventions can affect the regulation of insulin-like growth factor 1, and accelerate muscle growth and size.


Main Subjects





Compliance with ethical standards

Conflict of interest The authors declare that they have no conflict of interest.

Ethical approval This study was approved by the Ethical Standards of the Institutional and/or National Research Committee (SSRI.REC-2205-1628). 

Informed consent Animal study.

Author contributions

Conceptualization: F.K.S, F.Sh, M.S.; Methodology: F.K.S, F.Sh, M.S.; Software: F.K.S, F.Sh, M.S.; Validation: F.K.S, F.Sh, M.S.; Formal analysis: F.K.S, F.Sh, M.S.; Investigation: F.K.S, F.Sh, M.S.; Resources: F.K.S, F.Sh, M.S.; Data curation: F.K.S, F.Sh, M.S.; Writing - original draft: F.K.S, F.Sh, M.S.; Writing – review & editing: F.K.S, M.S.; Visualization: F.K.S, F.Sh, M.S.; Supervision: F.K.S.; Project administration: F.K.S, F.Sh, M.S.; Funding acquisition: F.K.S.

Ahmadi-Kani Golzar, F., R. Fathi and S. Mahjoub (2017). "The effects of endurance training and whey protein supplementation on inflammation and insulin resistance in the rats fed with high-fat diet." Scientific Journal of Kurdistan University of Medical Sciences 22(4): 80-90. doi:  https://doi.org/10.22102/22.4.80
Aram, Y., H. Jun-Young, C. Soon-Mi, H. Dong-Woo, K. Ki-Jeong and L. Suk-Ho (2015). "Comparison of multiple sets and progressive single set of resistance training on muscle mass and strength in rat." Exercise Science 24(3): 267-274. doi: https://doi.org/10.15857/ksep.2015.24.3.267
Askari, B., N. Bijeh and A. R. Lamir (2017). "Effects of 8 Weeks of Resistance Training and IGF-1 Injection on Biochemical Markers of Cancer and Colorectal Structures in Rats." Medical Laboratory Journal 11(6). doi:  https://doi.org/10.29252/mlj.11.6.S1
Chromiak, J. A. and J. Antonio (2002). "Use of amino acids as growth hormone-releasing agents by athletes." Nutrition 18(7-8): 657-661. doi:   https://doi.org/10.1016/S0899-9007(02)00807-9
Coffey, V. G. and J. A. Hawley (2017). "Concurrent exercise training: do opposites distract?" The Journal of physiology 595(9): 2883-2896. doi:  https://doi.org/10.1113/JP272881
Csapo, R., M. Gumpenberger and B. Wessner (2020). "Skeletal muscle extracellular matrix–what do we know about its composition, regulation, and physiological roles? A narrative review." Frontiers in physiology 11: 253. doi:  https://doi.org/10.3389/fphys.2020.00253
Deldicque, L. (2020). Protein intake and exercise-induced skeletal muscle hypertrophy: An Update, MDPI. 12: 2023. doi: https://doi.org/10 .3390/nu12072023
Gholipour, M., M. Seifabadi and M. R. Asad (2020). "Comparing the effects of endurance and resistance trainings on gene expression involved in protein synthesis and degradation signaling pathways of Wistar rat soleus muscle." Tehran University of Medical Sciences Journal 77(11): 668-677. doi:  http://tumj.tums.ac.ir/article-1-10197-en.html
Gorzi, A., R. Jazaei, A. Rahmani and A. Bahari (2019). "The effects of different rest interval durations between resistance exercise sets on gene expression of CGRP and IGF-1 of muscle in male wistar rats." Research in Sport Medicine and Technology 17(18): 23-33. doi:  https://doi.org/10.29252/jsmt.17.18.23
Gwin, J. A., D. D. Church, R. R. Wolfe, A. A. Ferrando and S. M. Pasiakos (2020). "Muscle protein synthesis and whole-body protein turnover responses to ingesting essential amino acids, intact protein, and protein-containing mixed meals with considerations for energy deficit." Nutrients 12(8): 2457. doi: https://doi.org/10.3390/nu12082457
Hall, J. E. and M. E. Hall (2020). Guyton and Hall textbook of medical physiology e-Book, Elsevier Health Sciences. ISBN: 9780323597128
Jang, J. H., S. Kim, H. J. Lee, H. J. Suh and K. Jo (2021). "Stimulating effect of whey protein hydrolysate on bone growth in MC3T3-E1 cells and a rat model." Food & Function 12(11): 5109-5117. doi: https://doi.org/10.1039/D1FO00338A
Kandil, N., D. A. Sabry, N. E. Ashry and H. I. El-Sayyad (2020). "Therapeutic Potential of Whey against Aging Related Cytological Damage of Adenohypophysis of Rat." sch. j. agric. life sci 3(8): 304-310. doi: https://doi.org/10.36349/EASJALS.2020.v03i09.002
Kashef, M. and S. Khaje Bahrami (2019). "The effect of 4 and 6 weeks of resistance training on serum levels of myonectin and IGF-1 in sedentary young men." Razi Journal of Medical Sciences 25(10): 31-37. doi:  https://doi.org/20.1001.1.22287043.1397.
Lam, F.-C., T. M. Khan, H. Faidah, A. Haseeb and A. H. Khan (2019). "Effectiveness of whey protein supplements on the serum levels of amino acid, creatinine kinase and myoglobin of athletes: a systematic review and meta-analysis." Systematic reviews 8(1): 1-12. doi: https://apastyle.apa.org/style-grammar-guidelines/references/dois-urls
Lednev, E. M., I. V. Kravchenko, V. A. Furalyov, E. A. Lysenko, I. S. Lemesheva, A. A. Grushin, V. E. Dubrov, O. L. Vinogradova and D. V. Popov (2020). "Effect of amino acids on IGF1 gene expression in human myotubes and skeletal muscle." Growth Hormone & IGF Research 53: 101323. doi: https://doi.org/10 .1016/j .ghir .2020 .101323
Li, M. and F. Liu (2019). "Effect of whey protein supplementation during resistance training sessions on body mass and muscular strength: a meta-analysis." Food & function 10(5): 2766-2773. doi:  https://doi.org/10.1039/c8fo02497j
Lin, Y.-A., Y.-R. Li, Y.-C. Chang, M.-C. Hsu and S.-T. Chen (2021). "Activation of IGF-1 pathway and suppression of atrophy related genes are involved in Epimedium extract (icariin) promoted C2C12 myotube hypertrophy." Scientific reports 11(1): 10790. doi: https://doi.org/10.1038/s41598-021-90281-w
Mori, H. and Y. Tokuda (2018). "Effect of whey protein supplementation after resistance exercise on the muscle mass and physical function of healthy older women: A randomized controlled trial." Geriatrics & gerontology international 18(9): 1398-1404. doi: https://doi.org/10 .1111/ggi .13449
Morisasa, M., E. Yoshida, M. Fujitani, K. Kimura, K. Uchida, T. Kishida, T. Mori and N. Goto-Inoue (2022). "Fish protein promotes skeletal muscle hypertrophy via the Akt/mTOR signaling pathways." Journal of Nutritional Science and Vitaminology 68(1): 23-31. doi: https://doi.org/10 .3177/jnsv .68 .23
Nasrollahi, H., A. A. Gaeini, S. Biglari and A. Ghardashi Afousi (2020). "Changes of insulin-like growth factor I gene expression in gastrocnemius muscle of male Wistar rats after a period of high-intensity interval training." Daneshvar Medicine 25(5): 31-38.
Rostamian Dolatshanlou, S., S. Cheragh-Birjandi and A. Yaghoubi (2023). "The Effects of Different Training on Gene Expression Involved in Muscle Autophagy in Elderly Rats." Journal of Isfahan Medical School 40(699): 1016-1022. doi: https://doi.org/10.48305/JIMS.V40.I699.1016
Sakuma, K. (2013). "Basic biology and current understanding of skeletal muscle." Nova Biomedical. ISBN9781628083675
Schoenfeld, B. J. (2020). Science and development of muscle hypertrophy, Human Kinetics. doi:  https://doi.org/10 .5040/9781492597668
Teixeira, F. J., H. O. Santos, S. L. Howell and G. D. Pimentel (2019). "Whey protein in cancer therapy: A narrative review." Pharmacological research 144: 245-256. doi:  https://doi.org/10 .1016/j .phrs .2019 .04 .025
Tiidus, P. M., A. R. Tupling and M. E. Houston (2012). Biochemistry primer for exercise science, Human kinetics. doi:  https://doi.org/10 .5040/9781492597668
Vitale, G., G. Pellegrino, M. Vollery and L. J. Hofland (2019). "Role of IGF-1 system in the modulation of longevity: controversies and new insights from a centenarians' perspective." Frontiers in endocrinology 10: 27. doi:   https://doi.org/10 .3389/fendo .2019 .00027
Wackerhage, H., J. Smith and D. Wisneiwski (2017). "Molecular exercise physiology." Oxford textbook of childrenVs sport and exercise medicine: 430-440. doi:   https://doi.org/10 .1093/med/9780198757672 .003 .0034
Wan, X., S. Wang, J. Xu, L. Zhuang, K. Xing, M. Zhang, X. Zhu, L. Wang, P. Gao and Q. Xi (2017). "Dietary protein-induced hepatic IGF-1 secretion mediated by PPARγ activation." PLoS One 12(3): e0173174. doi:  https://doi.org/10.1371/journal.pone.0173174  
West, D. W., S. Abou Sawan, M. Mazzulla, E. Williamson and D. R. Moore (2017). "Whey protein supplementation enhances whole body protein metabolism and performance recovery after resistance exercise: a double-blind crossover study." Nutrients 9(7): 735. doi:  https://doi.org/10 .3390/nu9070735