scholarly journals Impaired Function of Regulatory T Cells in Type 2 Diabetes Mellitus

2020 ◽  
Vol 4 (1) ◽  
pp. 1
Author(s):  
Rona Kartika ◽  
Heri Wibowo
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
T Cells ◽  
Type 2 Diabetes Mellitus ◽  
Regulatory T Cells ◽  
Inflammatory Response ◽  
Treg Cells ◽  
Low Grade

Pathogenesis of type 2 Diabetes Mellitus (DM) is often associated with chronic low-grade inflammation. This kind of inflammation is characterized by an increased level of pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin (IL)-6 and IL-1β. From an immunological point of view, an inflammatory response is always followed by an anti-inflammatory response as negative feedback to avoid excessive tissue damages. Regulatory T cells are a subset of cluster of differentiation (CD)4+ T cells that have the function to maintain peripheral tolerance and suppress immune response. This review would discuss the impaired function of regulatory T cells in type 2 DM. DM is a group of metabolic diseases characterized by hyperglycemia due to a defect of insulin secretion or a combination of insulin resistance and relative insulin deficiency. Chronic low-grade inflammation has been known as a key factor in the development of insulin resistance. Regulatory T cells (Treg cells) action through contact and non-contact inhibition could suppress inflammatory response in innate and adaptive immune systems. In type 2 DM, the proportion and function of CD4+CD25+Foxp3+ and CD4+CD25+ regulatory T cell decreases due to the reduced number of Treg cells and the Treg cells depletion contributes to metabolic conditions such as insulin resistance. Moreover, Treg cells are more susceptible to apoptosis, the ability of Treg cells to produce anti-inflammatory cytokines such as transforming growth factor β (TGF-β) and IL-10 decreases, and there is an imbalance between the proportion of Th1/Th17 cells and Treg cells. This inadequate anti-inflammatory response gives rise to the chronic low-grade inflammatory condition in type 2 DM.Keywords: type 2 diabetes mellitus, inflammation, regulatory T cell

scholarly journals Influence of metabolic disorders on phenotypic modulation of vascular endothelium in type 2 diabetes mellitus

2017 ◽  
Vol 70 (11-12) ◽  
pp. 437-443
Author(s):  
Romana Mijovic ◽  
Branislava Ilincic ◽  
Suncica Kojic-Damjanov ◽  
Biljana Vuckovic ◽  
Radmila Zeravica ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Adhesion Molecules ◽  
Vascular Endothelium ◽  
Low Grade ◽  
Phenotypic Modulation

Introduction. Endothelium is a dynamic, strategically positioned defensive regulator of vascular homeostasis. Physiology and Pathophysiology of Vascular Endothelium. Endothelial phenotypic modulation involves five basic characteristics: the expression of leukocyte adhesion molecules, the production of cytokines, change in the shape and the permeability of the endothelium, prothrombotic changes and upregulation of autoantigens. Obesity, Metabolic Inflammation and Vascular Endothelium One of the most important pathophysiological manifestations of adiposopathy may be the phenotypic conversion of vascular endothelium. Insulin Resistance and Vascular Endothelium. Under the conditions of insulin resistance and consequent hyperinsulinemia, there is imbalance between the production of endothelial vasoconstrictors and vasodilators, increased expression of adhesion molecules, and platelet hyperreactivity. Hyperglycemia and Vascular Endothelium. Hyperglycemia causes endothelial dysfunction by various mechanisms that involve activation of polyol pathway and production of sorbitol, increased formation of advanced glycation end products, activation of various isoforms of protein kinase C and activation of hexosamine pathway. Dyslipidemia and vascular endothelium. Dyslipidemia takes an important role in a cascade of pathophysiological processes that result in endothelial activation and chronic dysfunction. Conclusion. Hyperglycemia, hyperinsulinemia, insulin resistance, dyslipidemia, visceral obesity and low-grade inflammation are the main factors responsible for development of endothelial dysfunction in type 2 diabetes mellitus.

scholarly journals Elevated circulating effector memory T cells but similar levels of regulatory T cells in patients with type 2 diabetes mellitus and cardiovascular disease

2018 ◽  
Vol 16 (3) ◽  
pp. 270-280 ◽  
Author(s):  
Sara Rattik ◽  
Daniel Engelbertsen ◽  
Maria Wigren ◽  
Irena Ljungcrantz ◽  
Gerd Östling ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
T Cells ◽  
Type 2 Diabetes Mellitus ◽  
Regulatory T Cells ◽  
Memory T Cells ◽  
Effector Memory ◽  
Effector Memory T Cells

Type 2 diabetes mellitus is associated with an elevated risk of cardiovascular disease, but the mechanism through which diabetes contributes to cardiovascular disease development remains incompletely understood. In this study, we compared the association of circulating regulatory T cells, naïve T cells, effector memory T cells or central memory T cells with cardiovascular disease in patients with and without type 2 diabetes mellitus. Percentage of circulating T cell subsets was analysed by flow cytometry in type 2 diabetes mellitus subjects with and without prevalent cardiovascular disease as well as in non-diabetic subjects with and without prevalent cardiovascular disease from the Malmö SUMMIT cohort. Subjects with type 2 diabetes mellitus had elevated percentages of effector memory T cells (CD4+CD45RO+CD62L–; 21.8% ± 11.2% vs 17.0% ± 9.2% in non-type 2 diabetes mellitus, p < 0.01) and central memory T cells (CD4+CD45RO+CD62L+; 38.0% ± 10.7% vs 36.0% ± 9.5% in non-type 2 diabetes mellitus, p < 0.01). In contrast, the frequency of naïve T cells was reduced (CD4+CD45RO–CD62L+, 35.0% ± 16.5% vs 42.9% ± 14.4% in non-type 2 diabetes mellitus, p < 0.001). The proportion of effector memory T cells was increased in type 2 diabetes mellitus subjects with cardiovascular disease as compared to those without (26.4% ± 11.5% vs 18.4% ± 10.2%, p < 0.05), while no difference in regulatory T cells was observed between these two patient groups. This study identifies effector memory T cells as a potential cellular biomarker for cardiovascular disease among subjects with type 2 diabetes mellitus, suggesting a state of exacerbated immune activation in type 2 diabetes mellitus patients with cardiovascular disease.

scholarly journals Th17 and regulatory T cells in patients with different time of progression of type 2 diabetes mellitus

2020 ◽  
Vol 45 (1) ◽  
pp. 29-36 ◽  
Author(s):  
Juan Guzmán-Flores ◽  
Joel Ramírez-Emiliano ◽  
Victoriano Pérez-Vázquez ◽  
Sergio López-Briones
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
T Cells ◽  
Type 2 Diabetes Mellitus ◽  
Regulatory T Cells

scholarly journals The role of inflammation and macrophage accumulation in the development of obesity-induced type 2 diabetes mellitus and the possible therapeutic effects of long-chainn-3 PUFA

2010 ◽  
Vol 69 (2) ◽  
pp. 232-243 ◽  
Author(s):  
Elizabeth Oliver ◽  
Fiona McGillicuddy ◽  
Catherine Phillips ◽  
Sinead Toomey ◽  
Helen M. Roche
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Receptor ◽  
Insulin Signalling ◽  
Serine Phosphorylation ◽  
Therapeutic Effects ◽  
Low Grade

The WHO estimate that >1×106deaths in Europe annually can be attributed to diseases related to excess body weight, and with the rising global obesity levels this death rate is set to drastically increase. Obesity plays a central role in the metabolic syndrome, a state of insulin resistance that predisposes patients to the development of CVD and type 2 diabetes mellitus. Obesity is associated with low-grade chronic inflammation characterised by inflamed adipose tissue with increased macrophage infiltration. This inflammation is now widely believed to be the key link between obesity and development of insulin resistance. In recent years it has been established that activation of pro-inflammatory pathways can cross talk with insulin signalling pathways via a number of mechanisms including (a) down-regulation of insulin signalling pathway proteins (e.g. GLUT4 and insulin receptor substrate (IRS)-1), (b) serine phosphorylation of IRS-1 blocking its tyrosine phosphorylation in response to insulin and (c) induction of cytokine signalling molecules that sterically hinder insulin signalling by blocking coupling of the insulin receptor to IRS-1. Long-chain (LC)n-3 PUFA regulate gene expression (a) through transcription factors such as PPAR and NF-κB and (b) via eicosanoid production, reducing pro-inflammatory cytokine production from many different cells including the macrophage. LCn-3 PUFA may therefore offer a useful anti-inflammatory strategy to decrease obesity-induced insulin resistance, which will be examined in the present review.

scholarly journals Relationship between Th17 and regulatory T cells in patients with type 2 diabetes mellitus

2015 ◽  
Vol 6 ◽  
Author(s):  
Guzman-Flores Juan ◽  
Lopez-Briones Sergio ◽  
Pérez-Vázquez Victoriano ◽  
Ramírez-De Los Santos Saúl ◽  
López-Pulido Edgar
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
T Cells ◽  
Type 2 Diabetes Mellitus ◽  
Regulatory T Cells

scholarly journals Elevated Serum TNF-α Is Related to Obesity in Type 2 Diabetes Mellitus and Is Associated with Glycemic Control and Insulin Resistance

2020 ◽  
Vol 2020 ◽  
pp. 1-5 ◽  
Author(s):  
Hana Alzamil
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Chronic Inflammation ◽  
Affinity Column ◽  
Diabetic Patients ◽  
Low Grade ◽  
Model Assessment

Background. Diabetes and obesity are very common associated metabolic disorders that are linked to chronic inflammation. Leptin is one of the important adipokines released from adipocytes, and its level increases with increasing body mass index (BMI). Tumor necrosis factor alpha (TNF-α) is a cytokine that is released by adipocytes and inflammatory cells in response to chronic inflammation. Type 2 diabetes mellitus (T2DM) is believed to be associated with low-grade chronic inflammation. The current study aims to investigate the involvement of leptin and TNF-α in T2DM associated with obesity. Methodology. This is a cross-sectional study involving 63 healthy volunteers and 65 patients with T2DM. Body composition was measured, and fasting venous blood samples were analyzed for blood glucose, glycosylated hemoglobin (HbA1c), basal insulin, leptin, and TNF-α. HbA1c was measured by the affinity column method. Insulin, leptin, and TNF-α immunoassays were performed by the ELISA technique. Insulin resistance and beta-cell function were assessed using the homeostasis model assessment (HOMA-IR and HOMA-B). Results. Our study showed a significantly higher level of TNF-α in T2DM patients compared to controls (7.51 ± 2.48 and 6.19 ± 3.01, respectively; p=0.008). In obese diabetic patients, the serum level of TNF-α was significantly higher in comparison with nonobese diabetic patients (p<0.018) and obese nondiabetic group (p<0.001). TNF-α correlated positively with HbA1c (r = 0.361, p=0.003) and HOMA-IR (r = 0.296, p=0.017) in patients with T2DM. Conclusion. TNF-α is associated with concurrent obesity and T2DM and correlates with HbA1c. This suggests that TNF-α needs further investigation to explore if it has a role in monitoring the effectiveness of management in individuals with obesity and T2DM.

scholarly journals DR3 stimulation of adipose resident ILC2s ameliorates type 2 diabetes mellitus

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Pedram Shafiei-Jahani ◽  
Benjamin P. Hurrell ◽  
Lauriane Galle-Treger ◽  
Doumet Georges Helou ◽  
Emily Howard ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Death Receptor ◽  
Lymphoid Cells ◽  
Low Grade ◽  
Group 2

Abstract Disturbances in glucose homeostasis and low-grade chronic inflammation culminate into metabolic syndrome that increase the risk for the development of type 2 diabetes mellitus (T2DM). The recently discovered group 2 innate lymphoid cells (ILC2s) are capable of secreting copious amounts of type 2 cytokines to modulate metabolic homeostasis in adipose tissue. In this study, we have established that expression of Death Receptor 3 (DR3), a member of the TNF superfamily, on visceral adipose tissue (VAT)-derived murine and peripheral blood human ILC2s is inducible by IL-33. We demonstrate that DR3 engages the canonical and/or non-canonical NF-κB pathways, and thus stimulates naïve and co-stimulates IL-33-activated ILC2s. Importantly, DR3 engagement on ILC2s significantly ameliorates glucose tolerance, protects against insulin-resistance onset and remarkably reverses already established insulin-resistance. Taken together, these results convey the potent role of DR3 as an ILC2 regulator and introduce DR3 agonistic treatment as a novel therapeutic avenue for treating T2DM.

scholarly journals Changes of Regulatory T Cells and of Proinflammatory and Immunosuppressive Cytokines in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-19 ◽  
Author(s):  
Yong-chao Qiao ◽  
Jian Shen ◽  
Lan He ◽  
Xue-zhi Hong ◽  
Fang Tian ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
T Cells ◽  
Type 2 Diabetes Mellitus ◽  
Regulatory T Cells ◽  
Transforming Growth Factor ◽  
Meta Analysis ◽  
Elevated Serum ◽  
Serum Levels

Objective. The aim of this study was to investigate the changes of regulatory T cells (Treg), interleukin-6 (IL-6), IL-10, transforming growth factor-β(TGF-β), and tumor necrosis factor-alpha (TNF-α) in patients with type 2 diabetes mellitus (T2DM).Methods. We performed a comprehensive search up to July 2016 for all clinical studies about the changes of Treg, IL-6, IL-10, IL-17, TGF-β, and TNF-αin T2DM patients versus healthy controls.Results. A total of 91 articles (5642 cases and 7378 controls) were included for this meta-analysis. Compared with the controls (allp<0.001), the patients had increased serum levels of IL-6, TGF-β, and TNF-αbut decreased the percentage of peripheral CD4+CD25+Foxp3+Treg and serum IL-10 level. Furthermore, the percentage of peripheral CD4+CD25+Foxp3+Treg (p<0.001) and serum IL-10 level (p=0.033) were significantly lower in the patients with complication and in the patients without complication, respectively. No significant changes about the percentage of CD4+CD25+Treg (p=0.360) and serum IL-17 level (p=0.459) were found in T2DM patients.Conclusions. T2DM patients have decreased the percentage of peripheral CD4+CD25+Foxp3+Treg and levels of serum IL-10 but elevated serum levels of IL-6, TGF-β, and TNF-α. Presence of diabetic complications further lowers the peripheral CD4+CD25+Foxp3+Treg number.

scholarly journals Molecular biochemical aspects of salt (sodium chloride) in inflammation and immune response with reference to hypertension and type 2 diabetes mellitus

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Undurti N. Das
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Trace Elements ◽  
Type 2 Diabetes Mellitus ◽  
Essential Fatty Acids ◽  
Low Grade ◽  
Sodium Potassium ◽  
Tnf Α

AbstractObesity, insulin resistance, type 2 diabetes mellitus (T2DM) and hypertension (HTN) are common that are associated with low-grade systemic inflammation. Diet, genetic factors, inflammation, and immunocytes and their cytokines play a role in their pathobiology. But the exact role of sodium, potassium, magnesium and other minerals, trace elements and vitamins in the pathogenesis of HTN and T2DM is not known. Recent studies showed that sodium and potassium can modulate oxidative stress, inflammation, alter the autonomic nervous system and induce dysfunction of the innate and adaptive immune responses in addition to their action on renin-angiotensin-aldosterone system. These actions of sodium, potassium and magnesium and other minerals, trace elements and vitamins are likely to be secondary to their action on pro-inflammatory cytokines IL-6, TNF-α and IL-17 and metabolism of essential fatty acids that may account for their involvement in the pathobiology of insulin resistance, T2DM, HTN and autoimmune diseases.

scholarly journals The Inflammatory Marker HSCRP as a Predictor of Increased Insulin Resistance in Type 2 Diabetics without Atherosclerotic Manifestations

2019 ◽  
Vol 70 (5) ◽  
pp. 1791-1794
Author(s):  
Elena-Daniela Grigorescu ◽  
Victorita Sorodoc ◽  
Mariana Floria ◽  
Ecaterina Anisie ◽  
Alina Delia Popa ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Inflammatory Marker ◽  
Diabetic Patients ◽  
Low Grade ◽  
Type 2 Diabetic Patients ◽  
Care Plans

Low-grade inflammation is not only a specific feature in type 2 diabetes mellitus, but also a contributor to cardiovascular risk. Together with insulin resistance as the main characteristic of type 2 diabetes mellitus, subclinical imflammation maintains a vicious cycle of health-damaging processes. Our study assessed the inflammatory marker hsCRP in relation to the metabolic profiles of type 2 diabetic patients without clinical atherosclerotic manifestations. The results confirmed the hypothesized connection, which should be taken into consideration when designing and recommending diabetes care plans.

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