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

Mahabadi-Ashtiyani, Elham; Sheikh, Vida; Borzouei, Shiva; Salehi, Iraj; Alahgholi-Hajibehzad, Mahdi

doi:10.1007/s00011-019-01265-5

Cited by 19 publications

(12 citation statements)

References 38 publications

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“…Previous studies have demonstrated that T2DM impairs immune function, and this is associated with increased susceptibility to infections, autoimmune diseases, and cancer. Immunological alterations include reduced responsiveness of lymphocytes to environmental factors and excessive inflammatory response [5]. Moderate physical exercise is known to improve immune regulatory function in diabetic patients [31].…”

Section: Discussionmentioning

confidence: 99%

“…Excessive Th17 response (IL-17 and IL-22) that promotes impaired glucose utilization in the liver, muscle, and adipose tissue occurs in obese and insulin-resistant patients. In humans, Mahabadi-Ashtiyani et al also reported that IFN-γ and IL-17 secretion in PHA-stimulated lymphocyte cultures obtained from the blood of T2DM patients was higher, and IL-4 and IL-37 levels were lower in T2DM patients compared to the control volunteers [5]. Similarly, IL-17 promoted insulin signaling inhibition mediated by c-Jun kinase activation in the human liver [6].…”

Section: Introductionmentioning

confidence: 95%

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Recreational Dance Practice Modulates Lymphocyte Profile and Function in Diabetic Women

et al. 2020

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This study aimed to investigate the impact of a 16-week dance-based aerobic exercise program on lymphocyte function in healthy and type 2 diabetes mellitus (T2DM) women. We enrolled 23 women: 11 with T2DM and 12 non-diabetic controls. Initially, we performed anthropometry and body composition measurements, afterwards, plasma levels of C-reactive protein, lipids, and glucose were determined. We used flow cytometry to measure the CD25 and CD28 expression in circulating lymphocytes, T-regulatory (Treg) cell percentage, lymphocyte proliferation, and cytokines released by cultured lymphocytes. The T2DM group had a lower proportion of CD28+ cells and a higher percentage of Treg lymphocytes and proliferative capacity at the baseline compared with the control group. After 16 weeks of the program, differences in lymphocytes between the T2DM and the control groups disappeared. The dance program promoted IL-10 increase in both groups. We found decreased IL-4, IL-2, and IL-6 secretion in lymphocytes from the control group and increased IL-17 secretion and IL-10/IL-17 ratio in the T2DM group after the program. The program promoted marked changes in lymphocytes in diabetic women, leading to a balance between the different profiles.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Recreational Dance Practice Modulates Lymphocyte Profile and Function in Diabetic Women

et al. 2020

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“…Of note, the addition of sitagliptin or vitamin D 3 to the cultures led to decreased proliferation of CD4+ T cells and non-CD4+ cells isolated from both T2D patients and healthy controls. Sitagliptin in combination with vitamin D 3 was also more effective in suppressing cell proliferation, decreasing IL-17 production and enhancing the expression of the anti-inflammatory cytokine IL-37 by PBMCs [222].…”

Section: Synergistic Anti-inflammatory and Immunomodulatory Effects Of Vitamin D And Dpp-4 Inhibitors: Mechanistic Evidencementioning

confidence: 91%

“…A study conducted by Mahabadi-Ashtiyani et al [221] on PBMCs collected from T2D patients and healthy controls revealed that the addition to the culture of sitagliptin plus vitamin D 3 was more effective in reducing IL-6 and TNF-α production in both patients and controls, as compared to cultures treated with sitagliptin or vitamin D 3 alone. The same group recently demonstrated the in vitro ability of sitagliptin and vitamin D 3 to effectively suppress the increased T helper cell proliferation and inflammatory responses in patients with T2D [222]. Of note, the addition of sitagliptin or vitamin D 3 to the cultures led to decreased proliferation of CD4+ T cells and non-CD4+ cells isolated from both T2D patients and healthy controls.…”

Section: Synergistic Anti-inflammatory and Immunomodulatory Effects Of Vitamin D And Dpp-4 Inhibitors: Mechanistic Evidencementioning

confidence: 96%

Combination of vitamin D and dipeptidyl peptidase-4 inhibitors (VIDPP-4i) as an immunomodulation therapy for autoimmune diabetes

Pinheiro

Diniz

et al. 2021

International Immunopharmacology

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Type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA) represent the most common types of autoimmune diabetes and are characterized by different age of onset, degrees of immune-mediated destruction of pancreatic beta cells and rates of disease progression towards insulin dependence. Several immunotherapies aimed to counteract autoimmune responses against beta cells and preserve beta-cell function are currently being investigated, particularly in T1D. Preliminary findings suggest a potential role of combination therapy with vitamin D and dipeptidyl peptidase-4 (DPP-4) inhibitors (VIDPP-4i) in preserving beta-cell function in autoimmune diabetes. This manuscript aims to provide a comprehensive overview of the immunomodulatory properties of vitamin D and DPP-4 inhibitors, as well as the rationale for investigation of their combined use as an immunomodulation therapy for autoimmune diabetes.

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“…We also reported for the first time a remarkable clinical improvement after 3-year combination therapy with sitagliptin and vitamin D3 in a patient with mononeuritis multiplex, an unusual form of peripheral neuropathy characterized by the presence of perineuritis [90,91]. Recent in vitro and in vivo studies conducted in patients with T2D demonstrated that VIDPP-4i is able to: reduce the expression of pro-inflammatory cytokines (IFN-γ and IL-17); decrease the proliferation of CD4 + T cells and non-CD4 + cells; increase the levels of the anti-inflammatory cytokine IL-4; and upregulate the expression of IL-37 and FOXP3 (Forkhead box protein P3), which are well-known markers for regulatory T cells [92][93][94].…”

Section: Proposed Synergistic Effects Of Vitamin D and Dpp-4 Inhibitors In Covid-19mentioning

confidence: 99%

Cytokine Storm Modulation in COVID-19: A Proposed Role for Vitamin D and DPP-4 Inhibitor Combination Therapy (VIDPP-4i)

2021

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A dysregulated immune response characterized by the hyperproduction of several pro-inflammatory cytokines (a.k.a. ‘cytokine storm’) plays a central role in the pathophysiology of severe coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this Perspective article we discuss the evidence for synergistic anti-inflammatory and immunomodulatory properties exerted by vitamin D and dipeptidyl peptidase-4 (DPP-4) inhibitors, the latter being a class of antihyperglycemic agents used for the treatment of Type 2 diabetes, which have also been reported as immunomodulators. Then, we provide the rationale for investigation of vitamin D and DPP-4 inhibitor combination therapy (VIDPP-4i) as an immunomodulation strategy to ratchet down the virulence of SARS-CoV-2, prevent disease progression and modulate the cytokine storm in COVID-19.

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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

Cited by 19 publications

References 38 publications

Recreational Dance Practice Modulates Lymphocyte Profile and Function in Diabetic Women

Recreational Dance Practice Modulates Lymphocyte Profile and Function in Diabetic Women

Combination of vitamin D and dipeptidyl peptidase-4 inhibitors (VIDPP-4i) as an immunomodulation therapy for autoimmune diabetes

Cytokine Storm Modulation in COVID-19: A Proposed Role for Vitamin D and DPP-4 Inhibitor Combination Therapy (VIDPP-4i)

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