REGULATION OF L-ARGININE METABOLISM BY ANTI-INFLAMMATORY CYTOKINES IN PATIENTS WITH TYPE 1 DIABETES

Authors

DOI:

https://doi.org/10.11603/1811-2471.2026.v.i1.15704

Keywords:

type 1 diabetes mellitus, L-Arginine, arginase, endothelial NO synthase, anti-inflammatory cytokines

Abstract

SUMMARY. The study examines the specific effects of anti-inflammatory cytokines on the enzymatic pathways of L-arginine metabolism in patients with type 1 diabetes. It was found that decreased levels of the anti-inflammatory cytokines IL-4 and IL-10 are associated with suppression of the arginase pathway and activation of the NO-synthase pathway of arginine conversion.

The aim – to investigate the influence of anti-inflammatory cytokines on L-arginine metabolism under conditions of type 1 diabetes.

Material and Methods. 28 patients with type 1 diabetes were examined. The control group consisted of 15 practically healthy individuals of a similar age range.

Blood sampling was performed in the morning on an empty stomach from the cubital vein in a volume of 5 ml during the hospitalization of patients. The concentration of glucose in the blood was determined by the glucose oxidase method; normal values ​​were considered to be within the range of 3.5–6.0 mmol/l. In the blood serum of patients, the activity of endothelial NO synthase (eNOS), arginase activity, arginine concentration, and the level of anti-inflammatory cytokines IL-4 and IL-10 were determined by the enzyme-linked immunosorbent assay.

Results. In patients with type 1 diabetes, decreased levels of the anti-inflammatory cytokines IL-4 (by 43 %) and IL-10 (by 20 %) were observed, indicating activation of immunopathological processes. Arginase activity in blood serum decreased by 28 %, while eNOS activity increased by 33.4 %, accompanied by a 1.3-fold reduction in L-arginine levels. This indicates a predominance of the NO-synthase pathway of arginine conversion, which temporarily compensates for vascular dysfunction. The balance between arginase and eNOS activity is essential for support of vascular homeostasis in type 1 diabetes.

Conclusions. The decrease in IL-4 and IL-10 levels in type 1 diabetes promotes an increase in nitric oxide production due to activation of the NO-synthase pathway of arginine conversion, which allows partial alleviation of inflammatory endothelial damage even under conditions of chronic hyperglycemia.

References

Lespagnol E, Dauchet L, Pawlak-Chaouch M, Balestra C, Berthoin S, Feelisch M, Roustit M, Boissière J, Fontaine P, Heyman E. Early Endothelial Dysfunction in Type 1 Diabetes Is Accompanied by an Impairment of Vascular Smooth Muscle Function: A Meta-Analysis. Front Endocrinol (Lausanne). 2020;11:203. DOI: 10.3389/fendo.2020.00203. PMID: 32362871; PMCID: PMC7180178.

Dubsky M, Veleba J, Sojakova D, Marhefkova N, Fejfarova V, Jude EB. Endothelial Dysfunction in Diabetes Mellitus: New Insights. Int. J. Mol. Sci. 2023; 24, 10705. DOI: 10.3390/ijms241310705.

Xia Y, Chen W, Fu C, et al. Regulation of arginase activity and nitric oxide synthase by cytokines in diabetic vascular disease. Cytokine Growth Factor Rev. 2021; 58:71-82.

Nelin LD, Amin RH, Rannels DE. Arginase and endothelial nitric oxide synthase regulate nitric oxide production in bovine pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol. 2005;288(6): L1065-1072.

Wu D, Ren H, Li Y, et al. The interplay between arginase and nitric oxide synthase in endothelial dysfunction associated with diabetes mellitus. Oxid Med Cell Longev. 2019; 2019:1724740.

Khavrona OP, Biletska LP, Klyushta MYu. Vplyv prozapalnykh tsytokiniv na funktsionuvannya systemy L-Arhinin-NO u khvorykh na tsukrovyy diabet I typu [The influence of proinflammatory cytokines on the functioning of the L-Arginine-NO system in patients with type I diabetes]. Art of Medicine. 2025;2(34):86-90. Ukrainian. DOI: 10.21802/artm.2025.2.34.86

Sumbaev VV, Yasinskaya IM. Vliyanie DDT na aktivnost sintazy oksida azota v pecheni, legkikh i golovnom mozge krys [The effect of DDT on the activity of nitric oxide synthase in the liver, lungs, and brain of rats]. Sovremennye problemy toksikologii. 2000;3:3. Ukrainian.

Geyer J. W., Dabich D. Rapid method for determination of arginase activity in tissue homogenates. Anal Biochem. 1971. Vol. 39. P. 412–417.

Aleynikova TL, Rubtseva GV, Pavlova NA. Rukovodstvo k prakticheskim zanyatiyam po biohimii [Guide to Practical Classes in Biochemistry]. Meditsina. 2000: 128. Ukrainian.

Kaminitz A, Ash S, Askenasy N. Neutralization Versus Reinforcement of Proinflammatory Cytokines to Arrest Autoimmunity in Type 1 Diabetes. Clin Rev Allergy Immunol. 2017;52(3):460-472. DOI: 10.1007/s12016-016-8587-y.

Jhuma KA, Giasuddin AS, Hossain MS. Status of Serum Pro inflammatory Cytokines (IL-1, IL-6, TNF-α) and Anti-inflammatory Cytokines (IL-4, IL-10, IL-13) in Newly Diagnosed Bangladeshi Patients with Type 2 Diabetes Mellitus. Mymensingh Med J. 2023;32(4):1149-1155. PMID: 37777914.

Martinez FO, Gordon S, Locati M, Mantovani A. Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol. 2017;198(7):2932-2940.

Kim HJ, Lee S, Park JH, et al. The role of IL-10 in the regulation of endothelial function in diabetes: therapeutic implications. Int J Mol Sci. 2023;24(4):2456.

Collier JJ, Sparer TE, Karlstad MD, Burke SJ. Pancreatic islet inflammation: an emerging role for chemokines. J Mol Endocrinol. 2017;59(1):R33-R46. DOI: 10.1530/JME-17-0042.

Rath M, Müller I, Kropf P, et al. Metabolism via arginase or nitric oxide synthase: two competing arginine pathways in macrophages. Front Immunol. 2014; 5:532.

Modolell M, Corraliza IM, Link F, et al. Reciprocal regulation of the nitric oxide synthase/arginase balance in mouse macrophages by TH1 and TH2 cytokines. Eur J Immunol. 1995;25(4):1101-1104).

Bogdan C. Nitric oxide synthase in innate and adaptive immunity: an update. Trends Immunol. 2015; 36(3):161-178.

Romero MJ, Platt DH, Tawfik HE, et al. Diabetes-induced coronary vascular dysfunction involves increased arginase activity. Circulation. 2011;124(13): 1406-1415.

Published

2026-04-22

How to Cite

Biletska, L. P., & Khavrona, O. P. (2026). REGULATION OF L-ARGININE METABOLISM BY ANTI-INFLAMMATORY CYTOKINES IN PATIENTS WITH TYPE 1 DIABETES. Achievements of Clinical and Experimental Medicine, (1), 45–48. https://doi.org/10.11603/1811-2471.2026.v.i1.15704

Issue

Section

Original research articles
Received 2025-11-22
Accepted 2026-01-27
Published 2026-04-22