Anti-Inflammatory Effect of Combined Sitagliptin and Vitamin D3 on Cytokines Profile in Patients with Type 2 Diabetes Mellitus

Borzouei, Shiva; Sheikh, Vida; Ghasemi, Morteza; Zamani, Alireza; Telikani, Zahra; Zareighane, Zohre; Salehi, Iraj; Mozayanimonfared, Azadeh; Amirzargar, Mohammad Ali; Alahgholi-Hajibehzad, Mahdi

doi:10.1089/jir.2018.0144

Cited by 21 publications

(10 citation statements)

References 33 publications

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“…On the other hand, VIDPP-4i (vitamin D 3 1000 IU/day plus sitagliptin 100 mg/day) was associated with decreased IFN-γ, IL-17 and IL-21 production, downregulated expression of RORγt (a marker for Th17 cells) and BCL6 (a marker for T follicular helper cells), along with upregulated expression of IL-37 and FOXP3, which are well-known markers for Tregs [223]. Similar results have been observed in another study from the same group, showing that treatment with sitagliptin plus vitamin D 3 reduced the levels of IFN-γ and IL-17 in both non-nephropathic and nephropathic T2D patients compared to untreated patients [224]. IL-37 levels were enhanced in patients treated with sitagliptin or sitagliptin plus vitamin D 3 compared to untreated patients.…”

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

confidence: 77%

“…Moreover, treatment with sitagliptin plus vitamin D 3 increased IL-4 levels in non-nephropathic T2D patients. Overall, these findings suggest that treatment with sitagliptin plus vitamin D 3 is more effective in reducing the upregulation of the pro-inflammatory cytokines IFN-γ and IL-17 in patients with T2D [224]. According to the synergistic anti-inflammatory actions of vitamin D and DPP-4i, a recent study conducted in a rat model of fructose/salt-induced insulin resistance showed superadditive renoprotective effects evoked by the combined use of vitamin D 3 and vildagliptin, which reversed hyperuricemia and exerted a plethora of renal anti-inflammatory, antioxidant, anti-apoptotic and anti-fibrotic effects [225].…”

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

confidence: 75%

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

confidence: 77%

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

confidence: 75%

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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“…Notably, in the model of MD, the levels of anti-inflammatory IL-4 and IL-10, and TGF-1beta increase simultaneously with the concentration of pro-inflammatory mediators. The cells mainly responsible for secretion of TGF-1beta and IL-10 are alternatively polarized M2 macrophages that have been shown to contribute to resolution of inflammation, wound healing and tissue remodeling via paracrine effects (Borzouei et al, 2019). We postulate that in MD, the ratio between mediators of inflammation and antiinflammation should be considered.…”

Section: Discussionmentioning

confidence: 99%

Bisamide Derivative of Dicarboxylic Acid Contributes to Restoration of Testicular Tissue Function and Influences Spermatogonial Stem Cells in Metabolic Disorders

Пахомова

Першина

Nebolsin³

et al. 2020

Front. Cell Dev. Biol.

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Metabolic syndrome can lead to several challenging complications including degeneration of the pancreas and hypogonadism. Recently, we have shown that Bisamide Derivative of Dicarboxylic Acid (BDDA) can contribute to pancreatic restoration in mice with metabolic disorders via its positive effects on lipid and glucose metabolism, and by increasing the numbers of pancreatic stem cells. In the present study, we hypothesized that BDDA might also be effective in restoring hypogonadism caused by metabolic syndrome. Experiments were performed on male C57BL/6 mice with hypogonadism, where metabolic disorders have been introduced by a combination of streptozotocin treatment and high fat diet. Using a combination of histological and biochemical methods along with a flow cytometric analysis of stem and progenitor cell markers, we evaluated the biological effects of BDDA on testicular tissue, germ cells, spermatogonial stem cells in vitro and in vivo, as well as on fertility. We demonstrate that in mice with metabolic disorders, BDDA has positive effects on spermatogenesis and restores fertility. We also show that BDDA exerts its therapeutic effects by reducing inflammation and by modulating spermatogonial stem cells. Thus, our results suggest that BDDA could represent a promising lead compound for the development of novel therapeutics able to stimulate regeneration of the testicular tissue and to restore fertility in hypogonadism resulting from complications of metabolic syndrome.

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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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Anti-Inflammatory Effect of Combined Sitagliptin and Vitamin D3 on Cytokines Profile in Patients with Type 2 Diabetes Mellitus

Cited by 21 publications

References 33 publications

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

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

Bisamide Derivative of Dicarboxylic Acid Contributes to Restoration of Testicular Tissue Function and Influences Spermatogonial Stem Cells in Metabolic Disorders

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

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