Volume 27, Issue 4 (Avicenna Journal of Clinical Medicine-Winter 2021)
Avicenna J Clin Med 2021, 27(4): 193-200 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Moghimi H, Borzouei S, Zamani A, Behzad M. Evaluation of the Effect of Empagliflozin Therapy on T Helper 22 Cell-Related Factors in Patients with Type 2 Diabetes Mellitus. Avicenna J Clin Med 2021; 27 (4) :193-200
URL: http://sjh.umsha.ac.ir/article-1-2141-en.html
URL: http://sjh.umsha.ac.ir/article-1-2141-en.html
1- MSc in Immunology, Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
2- Associate Professor, Department of Internal Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
3- Professor, Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
4- Associate Professor, Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran ,m.behzad@umsha.ac.ir
2- Associate Professor, Department of Internal Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
3- Professor, Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
4- Associate Professor, Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran ,
Abstract: (2781 Views)
Background and Objective:The increased response of T helper (Th) 22cells might be involved in thepathogenesis ofType 2 Diabetes Mellitus (T2DM). The present study aimed to investigate the transcription factor of Th22 cells (aryl hydrocarbon receptor [AHR]) and interleukin 22 (IL-22) in CD4+ T cells as well as the impact of oral empagliflozin treatment. The correlation between the aforementioned factors and clinical parameters was also determined among the patients.
Materials and Methods:In this case-control study, 50 patients under the treatment of metformin and gliclazide were divided into two equal groups, including the patients receiving empagliflozin (EMPA+) and not receiving empagliflozin (EMPA, as the control group). The peripheral blood CD4+ T cells were isolated on the initiation day of the study and after 6 months of therapy, and the gene expression levels of AHR and IL-22 were evaluated by real-time polymerase chain reaction. In addition, the production of IL-22 after activation was measured using enzyme-linked immunosorbent assay.
Materials and Methods:In this case-control study, 50 patients under the treatment of metformin and gliclazide were divided into two equal groups, including the patients receiving empagliflozin (EMPA+) and not receiving empagliflozin (EMPA, as the control group). The peripheral blood CD4+ T cells were isolated on the initiation day of the study and after 6 months of therapy, and the gene expression levels of AHR and IL-22 were evaluated by real-time polymerase chain reaction. In addition, the production of IL-22 after activation was measured using enzyme-linked immunosorbent assay.
Results:The levels of fasting plasma glucose and hemoglobin A1c diminished in the EMPA+ group after empagliflozin therapy, compared to those reported at the baseline (initiation day; P<0.001 and P=0.04). The gene expression level of IL-22 and production of IL-22 significantly reduced after 6 months of empagliflozin therapy (P=0.011 and P=0.001). A significant positive correlation between IL-22 production and its gene expression with AHR as well as between fasting plasma glucose and hemoglobin A1c was observed in the EMPA+ patients after therapy (P˂0.05).
Conclusion:In addition to antidiabetic effects, empagliflozin has anti-inflammatory impacts on the immune system, especially on Th22 cell-related factors.
Type of Study: Original |
Subject:
Immunology
References
1. Zhou T, Hu Z, Yang S, Sun L, Yu Z, Wang G. Role of adaptive and innate immunity in type 2 diabetes mellitus.J Diabetes Res. 2018;2018:7457269. PMID: 30533447DOI: 10.1155/2018/7457269
2. Calle MC, Fernandez ML. Inflammation and type 2 diabetes.Diabetes Metab. 2012;38(3):183-91. PMID: 22252015DOI: 10.1016/j.diabet.2011.11.006
3. Kagami S, Rizzo HL, Lee JJ, Koguchi Y, Blauvelt A. Circulating Th17, Th22, and Th1 cells are increased in psoriasis.J Invest Dermatol. 2010;130(5):1373-83. PMID: 20032993DOI: 10.1038/jid.2009.399
4. Jia L, Wu C. The biology and functions of Th22 cells.Adv Exp Med Biol. 2014;841:209-30. PMID: 25261209DOI: 10.1007/978-94-017-9487-9_8
5. Zhao L, Jiang Z, Jiang Y, Ma N, Wang K, Zhang Y, et al. IL-22+CD4+ T-cellsin patients with active systemic lupus erythematosus.Exp Biol Med (Maywood). 2013;238(2):193-9. PMID: 23576801DOI: 10.1177/1535370213477597
6. da Rocha LF Jr, Duarte AL, Dantas AT, Mariz HA, Pitta Ida R, Galdino SL, et al. Increased serum interleukin 22 in patients with rheumatoid arthritis and correlation with disease activity.J Rheumatol. 2012;39(7):1320-5. PMID: 22589261DOI: 10.3899/jrheum.111027
7. Xu X, Zheng S, Yang F, Shi Y, Gu Y, Chen H, et al. Increased Th22 cells areindependently associated with Th17 cells in type 1 diabetes.Endocrine. 2014;46(1):90-8. PMID: 23928796DOI: 10.1007/s12020-013-0030-z
8. Zhao R, Tang D, Yi S, Li W, Wu C, Lu Y, et al. Elevated peripheral frequencies of Th22cells: a novel potent participant in obesity and type 2 diabetes.PLoS One. 2014;9(1):e85770. PMID: 24465695DOI: 10.1371/journal.pone.0085770
9. Guo H, Xu BC, Yang XG, Peng D, Wang Y, Liu X B, et al. A high frequency of peripheral blood IL-22(+) CD4(+) T cells in patients with new onset type 2 diabetes mellitus.J Clin Lab Anal. 2016;30(2):95-102. PMID: 25425169DOI: 10.1002/jcla.21821
10. Dalmas E, Venteclef N, Caer C, Poitou C, Cremer I, Aron-Wisnewsky J, et al. T cell-derived IL-22 amplifies IL-1β-driven inflammation in human adipose tissue: relevance to obesity and type 2 diabetes.Diabetes. 2014;63(6):1966-77. PMID: 24520123DOI: 10.2337/db13-1511
11. Fujita Y, Inagaki N. Metformin: new preparations and nonglycemic benefits.Curr Diab Rep. 2017;17(1):5. PMID: 28116648DOI: 10.1007/s11892-017-0829-8
12. Araújo AA, Morais HB, Medeiros C, Brito GA, Guedes PM, Hiyari S, et al. Gliclazide reduced oxidative stress, inflammation, and bone loss in an experimental periodontal disease model.J Appl Oral Sci. 2019;27:e20180211. PMID: 30810635DOI: 10.1590/1678-7757-2018-0211
13. Frampton JE. Empagliflozin: a review in type 2 diabetes.Drugs. 2018;78(10):1037-48. PMID: 29946963DOI: 10.1007/s40265-018-0937-z
14. Han JH, Oh TJ, Lee G, Maeng HJ, Lee DH, Kim KM, et al. The beneficial effects of empagliflozin, an SGLT2 inhibitor, on atherosclerosis in ApoE (-/-) mice fed a western diet.Diabetologia. 2017;60(2):364-76. PMID: 27866224DOI: 10.1007/s00125-016-4158-2
15. Iannantuoni F, Diaz-Morales N, Falcon R, Bañuls C, Abad-Jimenez Z, Victor VM, etal. The SGLT2 inhibitor empagliflozin ameliorates the inflammatory profile in type 2 diabetic patients and promotes an antioxidant response in leukocytes.J Clin Med. 2019;8(11):1814. PMID: 31683785DOI: 10.3390/jcm8111814
16. Telikani Z, Sheikh V,Zamani A, Borzouei S, Salehi I, Amirzargar MA, et al. Effects of sitagliptin and vitamin D3 on T helper cell transcription factors and cytokine production in clinical subgroups of type 2 diabetes mellitus: highlights upregulation of FOXP3 and IL-37.Immunopharmacol Immunotoxicol. 2019;41(2):299-311. PMID: 30907193DOI: 10.1080/08923973.2019.1593447
17. Jiang R, Wang H, Deng L, Hou J, Shi R, Yao M, etal. IL-22 is related to development of human colon cancerby activation of STAT3.BMC Cancer. 2013;13:59. PMID: 23379788DOI: 10.1186/1471-2407-13-59
18. Cheng L, Qian L, Tan Y, Wang GS, Li XM, Li XP, et al. Unbalanced expression of aryl hydrocarbon receptor in peripheral blood CCR6(+)CD4(+) and CD4(+)CD25(+) T cells of rheumatoid arthritis.Rev Bras Reumatol Engl Ed. 2017;57(3):190-6. PMID: 28535889DOI: 10.1016/j.rbre.2016.07.002
19. Hoseini-Aghdam M, Sheikh V, Eftekharian MM, Rezaeepoor M, Behzad M. Enhanced expression of TIGIT but not neuropilin-1in patients with type 2 diabetes mellitus.Immunol Lett. 2020;225:1-8. PMID: 32540486DOI: 10.1016/j.imlet.2020.06.003
20. Sabat R, Ouyang W, Wolk K. Therapeutic opportunities of the IL-22-IL-22R1 system.Nat Rev Drug Discov. 2014;13(1):21-38. PMID: 24378801DOI: 10.1038/nrd4176
21. Azizi G, Yazdani R, Mirshafiey A. Th22 cells in autoimmunity: a review of current knowledge.Eur Ann Allergy Clin Immunol. 2015;47(4):108-17. PMID: 26159476
22. Zhong W, Jiang Y, Ma H, Wu J, Jiang Z, Zhao L. Elevated levels of CCR6(+) T helper 22 cells correlate with skin and renal impairment in systemic lupus erythematosus.Sci Rep. 2017;7(1):12962. PMID: 29021537DOI: 10.1038/s41598-017-13344-w
23. Chen H, Wen F, Zhang X, Su SB. Expression of T-helper-associated cytokines in patients with type 2 diabetes mellitus with retinopathy.Mol Vis. 2012;18:219-26. PMID: 22312190
24. Gong F, Wu J, Zhou P, Zhang M, Liu J, Liu Y, et al. Interleukin-22 might act as a double-edged sword in type 2 diabetes and coronary artery disease.Mediators Inflamm. 2016;2016:8254797. PMID: 27829708DOI: 10.1155/2016/8254797
25. Ferrannini E, Muscelli E, Frascerra S, Baldi S, Mari A, Heise T, et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients.J Clin Invest. 2014;124(2):499-508. PMID: 24463454DOI: 10.1172/jci72227
26. Al Jobori H, Daniele G, Adams J, Cersosimo E, Solis-Herrera C, Triplitt C, etal. Empagliflozin treatment is associated with improved β-cell function in type 2 diabetes mellitus.J Clin Endocrinol Metab. 2018;103(4):1402-7. PMID: 29342295DOI: 10.1210/jc.2017-01838
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
Articles Copyright © The Author(s).
Owned by Hamadan University of Medical Sciences
Published by UMSHA Press
Journal Tel: +988138380924
Publisher Tel:+988138380548
Website: http://sjh.umsha.ac.ir
Email: s_ journal[at]umsha.ac.ir
