Association of NF-E2 Related Factor 2 (Nrf2) and inflammatory cytokines in recent onset Type 2 Diabetes Mellitus

Sireesh, Dornadula; Umapathy, Dhamodharan; Krishnamoorthy, Ezhilarasi; Viswanathan, Vijay; Ramkumar, Kunka Mohanram

doi:10.1038/s41598-018-22913-6

Cited by 97 publications

(75 citation statements)

References 45 publications

(64 reference statements)

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“…In contrast, polarization of anti-inflammatory Th2 cells was decreased [ 15 – 20 ]. A recent study [ 21 ] showed that Th1/Th2 ratio and levels of cytokines (e.g., IL-4, IL-10, IL-13, and IFN- γ ) were significantly elevated, whereas nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream targets, which act with antioxidant, detoxification, and maintenance of cellular redox homeostasis and glutathione homeostasis and influence mitochondrial biogenesis, were decreased in T2DM patients. The circulatory levels of Nrf2 showed a positive correlation with the levels of Th2 cytokines and negative correlation with the levels of Th1 cytokines [ 21 ].…”

Section: T Cells In T2dmmentioning

confidence: 99%

“…A recent study [ 21 ] showed that Th1/Th2 ratio and levels of cytokines (e.g., IL-4, IL-10, IL-13, and IFN- γ ) were significantly elevated, whereas nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream targets, which act with antioxidant, detoxification, and maintenance of cellular redox homeostasis and glutathione homeostasis and influence mitochondrial biogenesis, were decreased in T2DM patients. The circulatory levels of Nrf2 showed a positive correlation with the levels of Th2 cytokines and negative correlation with the levels of Th1 cytokines [ 21 ]. In addition, it showed that CD4+ and CD8+ T cells were infiltrated in both visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), with proinflammatory Th1 and Th17 cells significantly more frequent in VAT as compared with SAT.…”

Section: T Cells In T2dmmentioning

confidence: 99%

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Role of Adaptive and Innate Immunity in Type 2 Diabetes Mellitus

Zhou

Yang

et al. 2018

Journal of Diabetes Research

170

150

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After the recognition of the essential role of the immune system in the progression of type 2 diabetes mellitus, more studies are focused on the effects produced by the abnormal differentiation of components of the immune system. In patients suffering from obesity or T2DM, there were alterations in proliferation of T cells and macrophages, and impairment in function of NK cells and B cells, which represented abnormal innate and adaptive immunity. The abnormality of either innate immunity, adaptive immunity, or both was involved and interacted with each other during the progression of T2DM. Although previous studies have revealed the functional involvement of T cells in T2DM, and the regulation of metabolism by the innate or adaptive immune system during the pathogenesis of T2DM, there has been a lack of literature reviewing the relevant role of adaptive and innate immunity in the progression of T2DM. Here, we will review their relevant roles, aiming to provide new thought for the development of immunotherapy in T2DM.

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Section: T Cells In T2dmmentioning

confidence: 99%

Section: T Cells In T2dmmentioning

confidence: 99%

Role of Adaptive and Innate Immunity in Type 2 Diabetes Mellitus

Zhou

Yang

et al. 2018

Journal of Diabetes Research

170

150

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“…Some health-promoting compounds, like betanin, can interfere in the activation of transcriptional factors, i.e. the nuclear factor kappa B (NF-kB) and the factor 2 related to nuclear erythroid factor 2 (Nrf2), master regulators in homeostasis redox, which coordinate the RNA synthesis of numerous genes involved in inflammatory, cytoprotective and antioxidant responses (Siti, Kamisah, and Kamsiah 2015;Lingappan 2018;Liu et al 2019;Baird and Yamamoto 2020;Sireesh et al 2018;Sies, Berndt, and Jones 2017).…”

Section: Betanin Atherogenesis and Cardiovascular Diseasesmentioning

confidence: 99%

Betanin as a multipath oxidative stress and inflammation modulator: a beetroot pigment with protective effects on cardiovascular disease pathogenesis

Silva

Baião

Ferreira

et al. 2020

Critical Reviews in Food Science and Nutrition

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Oxidative stress is a common physiopathological condition enrolled in risk factors for cardiovascular diseases. Individuals in such a redox imbalance status present endothelial dysfunctions and inflammation, reaching the onset of heart disease. Phytochemicals are able to attenuate the main mechanisms of oxidative stress and inflammation and should be considered as supportive therapies to manage risk factors for cardiovascular diseases. Beetroot (Beta vulgaris L.) is a rich source of bioactive compounds, including betanin (betanidin-5-O-b-glucoside), a pigment displaying the potential to alleviate oxidative stress and inflammantion, as previously demonstrated in preclinical trials. Betanin resists gastrointestinal digestion, is absorbed by the epithelial cells of intestinal mucosa and reaches the plasma in its active form. Betanin displays free-radical scavenger ability through hydrogen or electron donation, preserving lipid structures and LDL particles while inducing the transcription of antioxidant genes through the nuclear factor erythroid-2-related factor 2 and, simultaneously, suppressing the pro-inflammatory nuclear factor kappa-B pathways. This review discusses the anti-radical and gene regulatory cardioprotective activities of betanin in the pathophysiology of endothelial damage and atherogenesis, the main conditions for cardiovascular disease. In addition, betanin influences on these multipath cellular signals and aiding in reducing cardiovascular disorders is proposed.

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“…Furthermore, it has been reported that interaction between Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2) can increase anti-inflammatory effects 8 . Previous reports have also reported that diabetes-induced inflammation and oxidative stress could induce intrinsic antioxidant response through the Keap1/Nrf2 pathway 9,10 . Incretin-related drugs decreased inflammatory status and enhanced Nrf2 system in DKD 11 .…”

mentioning

confidence: 92%

Linagliptin affects IRS1/Akt signaling and prevents high glucose-induced apoptosis in podocytes

Mima

Yasuzawa

Nakamura

et al. 2020

Sci Rep

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Diabetes-induced podocyte apoptosis is considered to play a critical role in the pathogenesis of diabetic kidney disease (DKD). We proposed that hyperglycaemia can induce podocyte apoptosis by inhibiting the action of podocyte survival factors, thus inactivating the cellular effects of insulin signalling. In this study, we aimed to determine the effects of linagliptin on high glucose-induced podocyte apoptosis. Linagliptin reduced the increase in DNA fragmentation as well as the increase in TUNEL-positive cells in podocytes induced by high-glucose condition. Furthermore, linagliptin improved insulin-induced phosphorylation of insulin receptor substrate 1 (IRS1) and Akt, which was inhibited in high-glucose conditions. Adenoviral vector-mediated IRS1 overexpression in podocytes partially normalised DNA fragmentation in high-glucose conditions, while downregulation of IRS1 expression using small interfering RNA increased DNA fragmentation even in low-glucose conditions. Because reactive oxygen species inhibit glomerular insulin signalling in diabetes and Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is one of the most important intrinsic antioxidative systems, we evaluated whether linagliptin increased Nrf2 in podocytes. Highglucose condition and linagliptin addition increased Nrf2 levels compared to low-glucose conditions. In summary, linagliptin offers protection against DKD by enhancing IRS1/Akt insulin signalling in podocytes and partially via the Keap1/Nrf2 pathway. Our findings suggest that linagliptin may induce protective effects in patients with DKD, and increasing IRS1 levels could be a potential therapeutic target in DKD.Diabetic kidney disease (DKD) is the most common cause of chronic kidney disease and end-stage renal disease (ESRD) 1 . Insulin/insulin receptor substrate-1 (IRS1) signalling can increase nitric oxide (NO) production, which is mediated by the PI3K/Akt pathway, thereby increasing anti-inflammatory effects 2 . NO induces vasodilatation and inhibits podocyte apoptosis 3 . Diabetes can inhibit insulin/IRS1 signalling in mesangial and glomerular endothelial cells, probably through the protein kinase C (PKC) β2 pathway 2 .Vascular endothelial growth factor (VEGF)-A can activate the anti-apoptotic proteins survivin or Bcl-2, thus decreasing endothelial cell apoptosis 4 . Insulin enhances VEGF-A expression, which in turn leads to increased Akt and eNOS phosphorylation, thus protecting against renal cell apoptosis. Furthermore, in our previous study, diabetes could increase podocyte apoptosis in DKD via activation of PKCδ/p38 mitogen-activated protein (MAPK) to enhance Src homology-2 domain containing phosphatase-1 (SHP-1) expression, which in turn resulted in VEGF resistance 5 . Thus, it is likely that the loss of effect of insulin on glomeruli may contribute to the development of DKD.Incretins are the family of gut hormones including glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide. Our recent study indicate...

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Association of NF-E2 Related Factor 2 (Nrf2) and inflammatory cytokines in recent onset Type 2 Diabetes Mellitus

Cited by 97 publications

References 45 publications

Role of Adaptive and Innate Immunity in Type 2 Diabetes Mellitus

Role of Adaptive and Innate Immunity in Type 2 Diabetes Mellitus

Betanin as a multipath oxidative stress and inflammation modulator: a beetroot pigment with protective effects on cardiovascular disease pathogenesis

Linagliptin affects IRS1/Akt signaling and prevents high glucose-induced apoptosis in podocytes

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