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 Potential Biomarkers of Insulin Resistance and Atherosclerosis in Type 2 Diabetes Mellitus Patients with Coronary Artery Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Sharifah Intan Qhadijah Syed Ikmal ◽  
Hasniza Zaman Huri ◽  
Shireene Ratna Vethakkan ◽  
Wan Azman Wan Ahmad
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Type 2 Diabetes Mellitus ◽  
Coronary Artery ◽  
Endothelial Dysfunction ◽  
Biological Marker ◽  
Artery Disease

Type 2 diabetes mellitus patients with coronary artery disease have become a major public health concern. The occurrence of insulin resistance accompanied with endothelial dysfunction worsens the state of atherosclerosis in type 2 diabetes mellitus patients. The combination of insulin resistance and endothelial dysfunction leads to coronary artery disease and ischemic heart disease complications. A recognized biological marker, high-sensitivity C-reactive protein, has been used widely to assess the progression of atherosclerosis and inflammation. Along with coronary arterial damage and inflammatory processes, high-sensitivity C-reactive protein is considered as an essential atherosclerosis marker in patients with cardiovascular disease, but not as an insulin resistance marker in type 2 diabetes mellitus patients. A new biological marker that can act as a reliable indicator of both the exact state of insulin resistance and atherosclerosis is required to facilitate optimal health management of diabetic patients. Malfunctioning of insulin mechanism and endothelial dysfunction leads to innate immune activation and released several biological markers into circulation. This review examines potential biological markers, YKL-40, alpha-hydroxybutyrate, soluble CD36, leptin, resistin, interleukin-18, retinol binding protein-4, and chemerin, as they may play significant roles in insulin resistance and atherosclerosis in type 2 diabetes mellitus patients with coronary artery disease.

scholarly journals Endothelial dysfunction and inflammatory biomarkers as a response factor of concurrent coenzyme Q10 add-on metformin in patients with type 2 diabetes mellitus

2019 ◽  
Vol 11 (04) ◽  
pp. 317-322
Author(s):  
Hayder M. Al-Kuraishy ◽  
Ali I. Al-Gareeb ◽  
Hala A. Shams ◽  
Farah Al-Mamorri
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Coenzyme Q10 ◽  
Healthy Subjects ◽  
Model Assessment ◽  
Inflammatory Changes

Abstract OBJECTIVES: The objective of the study was to evaluate the effect of metformin alone or in combination with coenzyme Q10 (CoQ10) on inflammatory changes and endothelial dysfunction in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: A total numbers of 54 patients with T2DM compared to 30 healthy subjects were divided into three groups: Group A (n = 30): healthy subjects without any medications; Group B (n = 24): T2DM patients treated with metformin 1 g/day; and Group C (n = 30): T2DM patients treated with metformin 1 g/day plus CoQ10, 300 mg/day. The duration of the study was 8 weeks. Fasting blood glucose, glycated hemoglobin, lipid profile, blood pressure variables, fasting insulin, insulin resistance, homeostatic model assessment of insulin resistance, vascular cell adhesion molecule 1 (VCAM-1), and E-selectin were measured before and after therapy. RESULTS: Metformin and/or CoQ10 therapy illustrated an insignificant effect on the fody mass index. This combination produced a significant improvement of metabolic changes in patients with T2DM (P < 0.01). sVCAM-1 serum level was decreased significantly after the initiation of metformin and/or CoQ10 therapy compared to the baseline P < 0.05. E-selectin was declined significantly following metformin monotherapy and after metformin plus CoQ10 therapy (P = 0.0001). CONCLUSION: CoQ10 add-on metformin therapy improves endothelial dysfunction and inflammatory changes in patients with T2DM alongside with amelioration of metabolic profile.

The clinical significance of insulin resistance, impaired carbohydrate and lipid metabolism in the development of microcirculation pathology in patients with chronic heart failure and type 2 diabetes mellitus

2016 ◽  
Vol 94 (6) ◽  
pp. 439-444
Author(s):  
Mihail E. Statsenko ◽  
S. V. Turkina ◽  
N. N. Shilina ◽  
M. A. Kosivtsova
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Chronic Heart Failure ◽  
Endothelial Dysfunction ◽  
Organ Damage ◽  
Carbohydrate And Lipid Metabolism

Patients with chronic heart failure and diabetes mellitus type 2 experience continuous progression of organ damage as a result of hemodynamic and metabolic disorders. An important role in pathogenesis of organ damage belongs to pathological types of microcirculation, endothelial dysfunction and insulin resistance. But the role of insulin resistance and its contribution to the formation of endothelial dysfunction and peculiarities of microcirculation in patients with chronic heart failure and type 2 diabetes mellitus is unknown. This study shows significant association between insulin resistance, disorders of carbohydrate and lipid metabolism, development of microcirculatory disturbances and endothelial dysfunction.

scholarly journals Histone deacetylase 3 inhibition alleviates type 2 diabetes mellitus-induced endothelial dysfunction via Nrf2

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shuai Huang ◽  
Gen Chen ◽  
Jia Sun ◽  
Yunjie Chen ◽  
Nan Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Histone Deacetylase ◽  
Vascular Endothelium ◽  
Ros Production ◽  
Histone Deacetylase 3

Abstract Background The mechanism underlying endothelial dysfunction leading to cardiovascular disease in type 2 diabetes mellitus (T2DM) remains unclear. Here, we show that inhibition of histone deacetylase 3 (HDAC3) reduced inflammation and oxidative stress by regulating nuclear factor-E2-related factor 2 (Nrf2), which mediates the expression of anti-inflammatory- and pro-survival-related genes in the vascular endothelium, thereby improving endothelial function. Methods Nrf2 knockout (Nrf2 KO) C57BL/6 background mice, diabetic db/db mice, and control db/m mice were used to investigate the relationship between HDAC3 and Nrf2 in the endothelium in vivo. Human umbilical vein endothelial cells (HUVECs) cultured under high glucose-palmitic acid (HG-PA) conditions were used to explore the role of Kelch-like ECH-associated protein 1 (Keap1) –Nrf2–NAPDH oxidase 4 (Nox4) redox signaling in the vascular endothelium in vitro. Activity assays, immunofluorescence, western blotting, qRT-PCR, and immunoprecipitation assays were used to examine the effect of HDAC3 inhibition on inflammation, reactive oxygen species (ROS) production, and endothelial impairment, as well as the activity of Nrf2-related molecules. Results HDAC3 activity, but not its expression, was increased in db/db mice. This resulted in de-endothelialization and increased oxidative stress and pro-inflammatory marker expression in cells treated with the HDAC3 inhibitor RGFP966, which activated Nrf2 signaling. HDAC3 silencing decreased ROS production, inflammation, and damage-associated tube formation in HG-PA-treated HUVECs. The underlying mechanism involved the Keap1–Nrf2–Nox4 signaling pathway. Conclusion The results of this study suggest the potential of HDAC3 as a therapeutic target for the treatment of endothelial dysfunction in T2DM.

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.

Liver alanine aminotransferase, insulin resistance and endothelial dysfunction in normotriglyceridaemic subjects with type 2 diabetes mellitus

2005 ◽  
Vol 35 (6) ◽  
pp. 369-374 ◽  
Author(s):  
R. K. Schindhelm ◽  
M. Diamant ◽  
S. J. L. Bakker ◽  
R. A. J. M. van Dijk ◽  
P. G. Scheffer ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Alanine Aminotransferase

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.

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