https://doi.org/10.4081/aiua.2025.14094
Effect of moderate-intensity aerobic exercise on penile α-SMA and eNOS expression in diabetes mellitus rats model: a non-pharmacological approach to diabetic erectile dysfunction
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Published: 28 August 2025
Background: Diabetes mellitus (DM) is a chronic disease with globally increasing prevalence, significantly impacting quality of life, including erectile dysfunction (ED). Moderate-intensity aerobic exercise has been shown to improve metabolic and cardiovascular parameters, yet limited studies have examined its effect on erectile function. This study aimed to explore the effect of aerobic exercise on the expression of alpha-smooth muscle actin (α-SMA) and endothelial nitric oxide synthase (eNOS) in the penile tissue of diabetic rat models.
Methods: This true-experimental study used 24 male Rattus norvegicus (Wistar), aged 12 weeks, randomly assigned to three groups: control (C), diabetic without intervention (NE), and diabetic with aerobic exercise (E). The aerobic exercise was performed for 60 minutes per session, 5 days a week, for 10 weeks. The expression of eNOS and α-SMA in penile tissues was analysed by immunohistochemistry and quantified by Image J Software Version 1.54p. Statistical analysis was performed using SPSS software version 29.0, including tests for homogeneity and normality, followed by one-way ANOVA with LSD or Tukey post-hoc tests for normally distributed data, or the Kruskal-Wallis test for non-normal distributions.
Results: There was no significant difference in eNOS expression among the three groups (p>0.05). However, α-SMA expression showed a significant difference among the three groups (p<0.05). Group E showed a significant increase in α-SMA expression compared to Group NE (p=0.034).
Conclusions: Moderate-intensity aerobic exercise improves α-SMA expression in the penile tissue of diabetic rats, contributing to better erectile function. Although it did not affect eNOS expression, this finding supports the potential of exercise-based non-pharmacological therapy for managing ED in diabetic patients.
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1. World Health Organization. Global Report on Diabetes. 2016. Available from: https://www.who.int/publications/i/item/9789241565257
2. Deshpande AD, Harris-Hayes M, Schootman M. Epidemiology of diabetes and diabetes-related complications. Phys Ther. 2008;88:1254-1264. DOI: https://doi.org/10.2522/ptj.20080020
3. Shlomai G, Neel B, LeRoith D, Gallagher EJ. Type 2 diabetes mellitus and cancer: the role of pharmacotherapy. J Clin Oncol. 2016;34:4261-4269. DOI: https://doi.org/10.1200/JCO.2016.67.4044
4. Lizza EF, Rosen RC. Definition and classification of erectile dysfunction: Report of the Nomenclature Committee of the International Society of Impotence Research. Int J Impot Res. 1999;11:141-143. DOI: https://doi.org/10.1038/sj.ijir.3900396
5. Gur S, C Peak T, J Kadowitz P, et al. Review of erectile dysfunction in diabetic animal models. Curr Diabetes Rev. 2014;10:61-73. DOI: https://doi.org/10.2174/1573399809666131126151024
6. Kyprianou N, Benning CM. Suppression of human prostate cancer cell growth by α1-adrenoceptor antagonists doxazosin and terazosinvia induction of apoptosis. Cancer Res. 2000; 60:4550-4555.
7. Su J, Lucchesi PA, Gonzalez-Villalobos RA, et al. Role of advanced glycation end products with oxidative stress in resistance artery dysfunction in type 2 diabetic mice. Arterioscler Thromb Vasc Biol. 2008;28:1432-1438. DOI: https://doi.org/10.1161/ATVBAHA.108.167205
8. Du XL, Edelstein D, Dimmeler S, et al. Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site. J Clin Invest. 2001; 108:1341-1348. DOI: https://doi.org/10.1172/JCI200111235
9. Neves D. Advanced glycation end-products: a common pathway in diabetes and age-related erectile dysfunction. Free Radic Res. 2013;47:S49-69. DOI: https://doi.org/10.3109/10715762.2013.821701
10. Christ M, Bauersachs J, Liebetrau C, et al. Glucose increases endothelial-dependent superoxide formation in coronary arteries by NAD(P)H oxidase activation. Diabetes. 2002; 51:2648-2652. DOI: https://doi.org/10.2337/diabetes.51.8.2648
11. Fauzi MF, Djojodimedjo T, Soebadi MA, Rahaju AS. Effects of telmisartan and moderated-intensity aerobic exercise on collagen type I expression in a diabetes melitus model. South East Eur J Public Health 2025:2242-2252.
12. Fatahajjad HH, Soebadi MA, Putra RM, et al. Effect of moderate-intensity aerobic exercise on bladder TGF-β1 and type I collagen expressions in diabetic rat model. Narra J. 2024;4:e1110-e1110. DOI: https://doi.org/10.52225/narra.v4i3.1110
13. Rajkovic J, Gostimirovic M, Bukarica A. Resveratrol and gut microbiota synergy: Preventive and therapeutic effects’. Int J Mol Sci. 2023; 24:17573. DOI: https://doi.org/10.3390/ijms242417573
14. Kaushal K, Sharma R, Patel A. Molecular mechanisms of erectile dysfunction in diabetes: Focus on oxidative stress and endothelial dysfunction. Int J Impot Res. 2024; 36:45-52.
15. Goncharov N V, Lokhmatova EY, Avdonin PV. Endothelial dysfunction in diabetes: The role of AGEs and NO signaling. J Vasc Biol. 2024; 56:22-30.
16. Wang T, Liu Y, Wang Y, et al. Irreversible erectile dysfunction in long-term diabetic rats: Failure of pharmacotherapy to reverse fibrosisand smooth muscle loss’. Andrology 2024; 8:1234-1242.
17. Shanaida M, Lysiuk R, Mykhailenko O. Alpha-lipoic acid: An antioxidant with anti-aging properties for disease therapy’. Curr Med Chem. 2025; 25:3708. DOI: https://doi.org/10.2174/0109298673300496240416114827
18. Kulawik T, Nowacki M, Dabrowski M. Moderate aerobic training prevents endothelial dysfunction and enhances eNOS expression in diabetic models. Diab Vasc Dis Res. 2024; 21:112-120.
19. Li Z, Yan Z. Effects of aerobic exercise on nitric oxide synthase and apelin in abdominal aorta of rats with type 2 diabetes mellitus. Asian Sports Science. 2014; 3:104-110.
20. Hicks S, Grijalva J, Zhao X, Medikayala S. Exercise training enhanced myocardial endothelial nitric oxide synthase (eNOS) function in diabetic Goto-Kakizaki (GK) rats’. Cardiovasc Res. 2008; 7:112-118. DOI: https://doi.org/10.1186/1475-2840-7-34
21. Zago AS, Reis Silveira L, Kokubun E. Effects of aerobic exercise on the blood pressure, oxidative stress and eNOS gene polymorphism in pre-hypertensive older people. Eur J Appl Physiol. 2010; 9:99-106. DOI: https://doi.org/10.1007/s00421-010-1568-6
22. Yin GN, Kim DK, Lee SH. Treadmill exercise prevents fibrosis and increases α-SMA in the corpora cavernosa of diabetic rats. Andrologia. 2018; 50:12805.
23. Liu G, Wang B, Wang L. Upregulation of TGF-β1 and α-SMA in diabetic cavernosal tissue: Indicators of fibrosis. J Sex Med. 2014;11:2343-2351.
24. Tao M, Tasdemir C, Tasdemir S, et al. Penile alterations at early stage of type 1 diabetes in rats’. Int Braz J Urol. 2017; 43:753-761. DOI: https://doi.org/10.1590/s1677-5538.ibju.2016.0454
25. Wang W, Liu Y, Zhu ZB, et al. Research advances in stem cell therapy for erectile dysfunction. BioDrugs 2024; 38:353-367. DOI: https://doi.org/10.1007/s40259-024-00650-9
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