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The increased T helper cells proliferation and inflammatory responses in patients with type 2 diabetes mellitus is suppressed by sitagliptin and vitamin D3 in vitro

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Abstract

Objective

The probably effects of sitagliptin and vitamin D3 (VitD3) on proliferation capacity and cytokines production were investigated in type 2 diabetes mellitus (T2DM) in vitro.

Materials and methods

Peripheral blood mononuclear cells (PBMCs) were isolated from 35 patients with T2DM and 26 healthy controls (HCs). CFSE-labeled PBMCs stimulated with phytohamagglutinin (PHA, 5 μg/mL) in the presence/absence of sitagliptin (200 mg/mL) with/without VitD3 (10−8 M) for 4 days. The proliferation of CD4+ T helper cells and non-CD4+ cells was analyzed using flow cytometry. The supernatant levels of IFN-γ, IL-17, IL-4, TGB-β and IL-37 were detected using ELISA.

Results

The proliferation of CD4+ T cells in response to PHA was higher in T2DM patients compared with HCs. The production of IFN-γ and IL-17 in PHA-stimulated cultures was higher, and the levels of IL-4 and IL-37 were lower in T2DM patients compared to HCs. The addition of sitagliptin or VitD3 to the cultures decreased the CD4+ T cells and non-CD4+ cells proliferation in patients and HCs. Sitagliptin with VitD3 was more effective in suppression of proliferation, decreasing of IL-17 and enhancing of IL-37 production.

Conclusion

Sitagliptin plus VitD3 effectively reduces the proliferative T cells response and modulates pro-inflammatory/anti-inflammatory cytokines production.

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Acknowledgements

We are grateful to our study participants. The study was funded by Vice-chancellor for Research and Technology, Hamadan University of Medical Sciences, Hamadan, Iran (No. 9608165137). E. M. A. and M. A. H. performed the experiments and analyzed the data. V. Sh., and Sh. B. took care of the donors. I. S. and M. A. H. contributed to the conceptualization of the manuscript. E. M. A. and M. A. H. produced the figures. E. M. A. and M. A. H. wrote the paper. All authors have approved the final manuscript.

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Authors and Affiliations

  1. Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Elham Mahabadi-Ashtiyani & Mahdi Alahgholi-Hajibehzad

  2. Department of Internal Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Vida Sheikh & Shiva Borzouei

  3. Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

    Iraj Salehi

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  1. Elham Mahabadi-Ashtiyani
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Correspondence to Mahdi Alahgholi-Hajibehzad.

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Mahabadi-Ashtiyani, E., Sheikh, V., Borzouei, S. et al. The increased T helper cells proliferation and inflammatory responses in patients with type 2 diabetes mellitus is suppressed by sitagliptin and vitamin D3 in vitro. Inflamm. Res. 68, 857–866 (2019). https://doi.org/10.1007/s00011-019-01265-5

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