Effects of Diabetes on the Kidney: Analysis of IL-2 and IL-10 Levels, Serum Glucose Levels, and Histopathological Findings

Abstract

This study aimed to investigate the effects of experimentally induced diabetes on renal tissue by evaluating biochemical parameters, cytokine levels (IL-2 and IL-10), and histopathological alterations in rats. Twelve adult male Wistar albino rats were used and randomly divided into control and diabetic groups. Experimental diabetes was induced by a single intraperitoneal injection of streptozotocin (65 mg/kg). At the end of the experimental period, kidney tissues and serum samples were collected under anesthesia. Serum glucose levels were measured to confirm diabetes induction. Renal IL-2 and IL-10 levels were determined using ELISA. Histopathological evaluation of kidney tissues was performed using Hematoxylin–Eosin and Masson’s Trichrome staining and tissue damage was assessed semi-quantitatively. Serum glucose levels were significantly elevated in the diabetic group compared to the control group (p < 0.01). Renal cytokine analysis demonstrated a significant decrease in both IL-2 and IL-10 levels in diabetic rats (p < 0.01). Histopathological examination revealed marked structural alterations in the diabetic group, including degeneration of renal corpuscles, tubular epithelial degeneration, vascular congestion, and perivascular fibrotic scar formation. In contrast, the control group exhibited normal renal histological architecture. Experimental diabetes induced by streptozotocin leads to significant biochemical, immunological, and histopathological changes in renal tissue. The observed decrease in both pro- and anti-inflammatory cytokines suggests impaired immune regulation, which may contribute to the development of diabetic kidney injury. These findings highlight the role of cytokine imbalance in the pathogenesis of diabetic nephropathy.

Keywords

• Experimental diabetes
• diabetic nephropathy
• inflammation
• streptozotocin

Supporting Institution

Kırşehir Ahi Evran University

Project Number

None

Ethical Statement

This study has been approved by the Clinical Researches Ethics Committee of Kırşehir Ahi Evran University (Date: 11.12.2025, Decision No: 24-01).

Thanks

We would like to thank Davut Yolcu and Yeliz Yolcu for their technical support

Diyabetin Böbrek Üzerine Etkileri: IL-2 ve IL-10 Düzeyleri, Serum Glukoz Düzeyleri ile Histopatolojik Bulguların Analizi

Abstract

Bu çalışmanın amacı, deneysel olarak oluşturulan diyabetin böbrek dokusu üzerindeki etkilerini; biyokimyasal parametreler, sitokin düzeyleri (IL-2 ve IL-10) ve histopatolojik değişiklikler açısından incelemektir. Çalışmada yirmi sekiz adet erişkin erkek Wistar albino sıçan kullanılmış ve rastgele kontrol ve diyabetik gruplara ayrılmıştır. Deneysel diyabet, tek doz intraperitoneal streptozotosin (65 mg/kg) enjeksiyonu ile oluşturulmuştur. Deney süresinin sonunda, anestezi altında böbrek dokuları ve serum örnekleri toplanmıştır. Diyabet oluşumunu doğrulamak amacıyla serum glukoz düzeyleri ölçülmüştür. Böbrek dokusunda IL-2 ve IL-10 düzeyleri ELISA yöntemi ile belirlenmiştir. Böbrek dokularının histopatolojik değerlendirmesi Hematoksilen-Eozin ve Masson’un Trikrom boyamaları ile yapılmış ve doku hasarı yarı kantitatif olarak değerlendirilmiştir. Diyabetik grupta serum glukoz düzeylerinin kontrol grubuna göre anlamlı derecede arttığı bulunmuştur (p < 0.01). Böbrek sitokin analizinde, diyabetik sıçanlarda hem IL-2 hem de IL-10 düzeylerinde anlamlı azalma tespit edilmiştir (p < 0.01). Histopatolojik incelemede diyabetik grupta belirgin yapısal değişiklikler gözlenmiş olup; renal korpüsküllerde dejenerasyon, tübüler epitel dejenerasyonu, vasküler konjesyon ve perivasküler fibrotik skar oluşumu saptanmıştır. Buna karşılık kontrol grubunda normal böbrek histolojik yapısı korunmuştur. Streptozotosin ile oluşturulan deneysel diyabet, böbrek dokusunda önemli biyokimyasal, immünolojik ve histopatolojik değişikliklere yol açmaktadır. Hem proinflamatuvar hem de antiinflamatuvar sitokinlerde gözlenen azalma, immün düzenlemenin bozulduğunu göstermekte ve bu durum diyabetik böbrek hasarının gelişimine katkıda bulunabilir. Bu bulgular, diyabetik nefropatinin patogenezinde sitokin dengesizliğinin rolünü vurgulamaktadır.

Keywords

• Deneysel diyabet
• diyabetik nefropati
• inflamasyon
• streptozotosin

Supporting Institution

Kırşehir Ahi Evran University

Project Number

None

Ethical Statement

Bu çalışma, Kırşehir Ahi Evran Üniversitesi Klinik Araştırmalar Etik Kurulu tarafından onaylanmıştır (Tarih: 11.12.2025, Karar No: 24-01).

Thanks

Davut Yolcu ve Yeliz Yolcu' nun teknik destekleri için teşekkür ederiz

References

1. Aborehab, N.M., El Bishbishy, M.H., Refaiy, A., & Waly, N.E. (2017). A putative Chondroprotective role for IL-1β and MPO in herbal treatment of experimental osteoarthritis. BMC Complement Altern Med, 17(1), 495. https://doi.org/10.1186/s12906-017-2002-y
2. Asif, R., Khalid, A., Mercantepe, T., Klisic, A., Rafaqat, S., Rafaqat, S., & Mercantepe, F. (2025). Role of interleukins in type 1 and type 2 diabetes. Diagnostics, 15(15), 1906. https://doi.org/10.3390/diagnostics15151906
3. Caliskan, H., Akat, F., Tatar, Y., Zaloglu, N., Dursun, A.D., Bastug, M., & Ficicilar, H. (2019). Effects of exercise training on anxiety in diabetic rats. Behavioural brain research, 376, 112084. https://doi.org/10.1016/j.bbr.2019.112084
4. Furman, B.L. (2015). Streptozotocin‐induced diabetic models in mice and rats. Current protocols in pharmacology, 70(1), 5-47. https://doi.org/10.1002/0471141755.ph0547s70
5. Genitsaridi, I., Salpea, P., Salim, A., Sajjadi, S.F., Tomic, D., James, S., Thirunavukkarasu, S., Issaka, A., Chen, L., & Basit, A. (2026). 11th edition of the IDF Diabetes Atlas: global, regional, and national diabetes prevalence estimates for 2024 and projections for 2050. The Lancet Diabetes & Endocrinology, 14(2), 149–156. https://doi.org/10.1016/S2213-8587(25)00299-2
6. Ghaderian, S.B., Hayati, F., Shayanpour, S., & Mousavi, S.S.B. (2015). Diabetes and end-stage renal disease; a review article on new concepts. Journal of renal injury prevention, 4(2), 28. https://doi.org/10.12861/jrip.2015.07
7. Ghasemi, A., & Jeddi, S. (2023). Streptozotocin as a tool for induction of rat models of diabetes: a practical guide. EXCLI journal, 22, 274. https://doi.org/10.17179/excli2022-5720
8. Guven, C., Koçak, S., Karadag, A., Aydın, H., Yalcin, A., & Turk, A. (2025). Adropin as a protective agent against renal ischemia-reperfusion injury induced by suprarenal aortic cross-clamping in rats. BMC nephrology, 26(1), 154. https://doi.org/10.1186/s12882-025-04087-2

9. Harris, A., & Patel, P. (2025). Interleukin. In StatPearls. StatPearls Publishing.
10. Huo, L., Zhang, H., Hou, S., Li, W., Meng, Q., Li, C., Ma, X., Huang, L., He, J., & Zhao, B. (2025). Low-dose IL-2 restores metabolic dysfunction and immune dysregulation in mice with type 2 diabetes induced by a high-fat, high-sugar diet and streptozotocin. International Journal of Biological Macromolecules, 286, 138468. https://doi.org//10.1016/j.ijbiomac.2024.138468
11. Ji, Y., Zhao, Z., Yang, Y., Wang, X., Qiao, R., Yu, X., Gong, X., Feng, Z., & Hong, Q. (2025). Mechanisms underlying the impact of interleukin family on acute kidney injury: pathogenesis, progression, and therapy. Research, 8, 0738. https://doi.org//10.34133/research.0738
12. Kalkan, K.T., & Pektas, F. (2026). Monosodium Glutamate Exposure and Liver Damage: Modulatory Effects of L‐Carnitine on Inflammation and Autophagy. Journal of Applied Toxicology, 46(4), 1361–1371. https://doi.org/10.1002/jat.70045
13. Mahlangu, T., Dludla, P.V., Nyambuya, T.M., Mxinwa, V., Mazibuko-Mbeje, S.E., Cirilli, I., Marcheggiani, F., Tiano, L., Louw, J., & Nkambule, B.B. (2020). A systematic review on the functional role of Th1/Th2 cytokines in type 2 diabetes and related metabolic complications. Cytokine, 126, 154892. https://doi.org/10.1016/j.cyto.2019.154892
14. Mensah-Brown, E., Obineche, E., Galadari, S., Chandranath, E., Shahin, A., Ahmed, I., Patel, S., & Adem, A. (2005). Streptozotocin-induced diabetic nephropathy in rats: the role of inflammatory cytokines. Cytokine, 31(3), 180–190. https://doi.org/10.1016/j.cyto.2005.04.006
15. Mohany, M., Alanazi, A.Z., Alqahtani, F., Belali, O.M., Ahmed, M.M., & Al-Rejaie, S.S. (2020). LCZ696 mitigates diabetic-induced nephropathy through inhibiting oxidative stress, NF-κB mediated inflammation and glomerulosclerosis in rats. PeerJ, 8, e9196. https://doi.org/10.7717/peerj.9196
16. Nasri, H., & Rafieian-Kopaei, M. (2015). Diabetes mellitus and renal failure: Prevention and management. Journal of research in medical sciences, 20(11), 1112–1120. https://doi.org/10.4103/1735-1995.172845
17. Sabapathy, V., Stremska, M.E., Mohammad, S., Corey, R.L., Sharma, P.R., & Sharma, R. (2019). Novel immunomodulatory cytokine regulates inflammation, diabetes, and obesity to protect from diabetic nephropathy. Frontiers in Pharmacology, 10, 572. https://doi.org/10.3389/fphar.2019.00572
18. Syed Khaja, A.S., Binsaleh, N.K., Beg, M.M. A., Ashfaq, F., Khan, M.I., Almutairi, M.G., Qanash, H., Saleem, M., & Ginawi, I.A.M. (2024). Clinical importance of cytokine (IL-6, IL-8, and IL-10) and vitamin D levels among patients with Type-1 diabetes. Scientific reports, 14(1), 24225. https://doi.org/10.1038/s41598-024-73737-6
19. Tesch, G.H., & Allen, T.J. (2007). Rodent models of streptozotocin‐induced diabetic nephropathy (Methods in Renal Research). Nephrology, 12(3), 261–266. https://doi.org/10.1111/j.1440-1797.2007.00796.x
20. Wenbin, Z., & Guojun, G. (2014). Resveratrol ameliorates diabetes-induced renal damage through regulating the expression of TGF-β1, collagen IV and Th17/Treg-related cytokines in rats. The West Indian Medical Journal, 63(1), 20. https://doi.org/10.7727/wimj.2014.008
21. Yang, M., & Zhang, C. (2024). The role of innate immunity in diabetic nephropathy and their therapeutic consequences. Journal of Pharmaceutical Analysis, 14(1), 39–51. https://doi.org/10.1016/j.jpha.2023.09.003
22. Yachmaneni Akanksha Jr., A., Jajoo, Suhas, S., Mahakalkar, Chandrashekhar, C., Kshirsagar, Shivani, S., & Dhole, Simran, S. (2023). A comprehensive review of the vascular consequences of diabetes in the lower extremities: Current approaches to management and evaluation of clinical outcomes. Cureus, 15(10), e47525. https://doi.org/10.7759/cureus.47525
23. Zhang, W., Liu, W., Leng, F., Shen, M., & Xie, J. (2025). Dietary non-starch plant polysaccharides: Multi-mechanisms for managing diabetic microvascular complications. Carbohydrate Polymers, 124074. https://doi.org/10.1016/j.carbpol.2025.124074