scholarly journals Intrinsic disorder in biomarkers of insulin resistance, hypoadiponectinemia, and endothelial dysfunction among the type 2 diabetic patients

2015 ◽  
Author(s):  
Osama H. Jiffri ◽  
Fadwa M. Al-Sharif ◽  
Essam H. Jiffri ◽  
Vladimir N. Uversky
Keyword(s):  
Insulin Resistance ◽  
Endothelial Dysfunction ◽  
Adhesion Molecule ◽  
Intrinsic Disorder ◽  
Cellular Adhesion ◽  
Diabetic Patients ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Cellular Adhesion Molecule

Type 2 diabetes mellitus (T2DM) is a chronic and progressive disease that is strongly associated with the all-cause and cardiovascular mortality. The present study aimed to analyze the abundance and functionality of intrinsically disordered regions in several biomarkers of insulin resistance, adiponectin, and endothelial dysfunction found in the T2DM patients. In fact, in comparison to controls, obese T2DM patients are known to have significantly higher levels of inter-cellular adhesion molecule (iCAM-1), vascular cell adhesion molecule (vCAM-1), and E-selectin, whereas their adiponectin levels are relatively low. Bioinformatics analysis revealed that these selected biomarkers (iCAM-1, vCAM-1, E-selectin, and adiponectin) are characterized by the noticeable levels of intrinsic disorder propensity and high binding promiscuity, which are important features expected for proteins serving as biomarkers. Within the limit of studied groups, there is an association between insulin resistance and both hypoadiponectinemia and endothelial dysfunction.

scholarly journals Intrinsic disorder in biomarkers of insulin resistance, hypoadiponectinemia, and endothelial dysfunction among the type 2 diabetic patients

2015 ◽  
Author(s):  
Osama H. Jiffri ◽  
Fadwa M. Al-Sharif ◽  
Essam H. Jiffri ◽  
Vladimir N. Uversky
Keyword(s):  
Insulin Resistance ◽  
Endothelial Dysfunction ◽  
Adhesion Molecule ◽  
Intrinsic Disorder ◽  
Cellular Adhesion ◽  
Diabetic Patients ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Cellular Adhesion Molecule

Type 2 diabetes mellitus (T2DM) is a chronic and progressive disease that is strongly associated with the all-cause and cardiovascular mortality. The present study aimed to analyze the abundance and functionality of intrinsically disordered regions in several biomarkers of insulin resistance, adiponectin, and endothelial dysfunction found in the T2DM patients. In fact, in comparison to controls, obese T2DM patients are known to have significantly higher levels of inter-cellular adhesion molecule (iCAM-1), vascular cell adhesion molecule (vCAM-1), and E-selectin, whereas their adiponectin levels are relatively low. Bioinformatics analysis revealed that these selected biomarkers (iCAM-1, vCAM-1, E-selectin, and adiponectin) are characterized by the noticeable levels of intrinsic disorder propensity and high binding promiscuity, which are important features expected for proteins serving as biomarkers. Within the limit of studied groups, there is an association between insulin resistance and both hypoadiponectinemia and endothelial dysfunction.

Abstract 18673: JNK Inhibition Restores Endothelial Function in Type 2 Diabetes Mellitus

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Rosa Breton-Romero ◽  
Bihua Feng ◽  
Monika Holbrook ◽  
Melissa G Farb ◽  
Jessica L Fetterman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Diabetic Patients ◽  
Jnk Activation

Introduction: Diabetes mellitus type 2 is an increasingly public health problem and it is a major cause in the development of cardiovascular diseases. Endothelial dysfunction is a key mechanism that contributes to the pathogenesis of cardiovascular diseases and is a well-known feature of clinical diabetes. Prior studies have demonstrated an impaired nitric oxide bioavailability and a reduced endothelium-dependent vasodilation under diabetic conditions and in animal models, JNK activity has been widely described to be involved in systemic insulin resistance. Hypothesis: Our study aimed to evaluate the involvement of JNK in endothelial dysfunction, studying its potential role in altered eNOS activation and NO synthesis in diabetic patients. Methods: We measured endothelial function and JNK activity in freshly isolated endothelial cells from diabetic patients (n=38) and nondiabetic controls (n=40). Results: ECs from diabetic patients displayed impaired eNOS activation and reduced NO release after insulin and A23187 stimulation, consistent with the presence of endothelial dysfunction. JNK activation was higher in diabetic (**P=0.003), and was associated with lower flow-mediated dilation (r=-0.53, *P=0.02). In endothelial cells from diabetic patients, treatment with JNK chemical inhibitor (SP600125) restored eNOS activation and insulin response (***P<0.001). Nitric oxide bioactivity after A23187 stimuli with diabetes was also recovered in endothelial cells from patients with diabetes. Conclusions: In summary, our data suggest that JNK activation contributes to vascular insulin resistance and endothelial dysfunction in patients with type 2 diabetes and may represent a target in novel therapeutic opportunities.

scholarly journals Markers of inflammation in patents with type 2 diabetes and cardiovascular form of diabetic autonomous neuropathy

2009 ◽  
Vol 12 (4) ◽  
pp. 51-55
Author(s):  
Irina Arkad'evna Bondar' ◽  
Olesya Yur'evna Shabel'nikova
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Endothelial Dysfunction ◽  
Resistance Index ◽  
Insulin Level ◽  
Diabetic Patients ◽  
Inflammation Markers ◽  
Markers Of Inflammation ◽  
Co Morbidity

Aim. To determine the level of inflammation markers and their relation to endothelial dysfunction and insulin resistance in patents with type 2 diabetesmellitus and cardiovascular form of diabetic autonomous neuropathy. Materials and methods. A total of 87 patients aged 45-66 years were examined for blood insulin level, insulin resistance index (HOMA-IR), CRP,and anti-inflammatory cytokine (TNF-a, IL-1-beta, IL-6) levels. Endothelial dysfunction was estimated based on quantitative Willebrand factorassay. Vegetative disorders were detected from reflex cardiovascular ECG data. Results. The development of cardiovascular form of diabetic autonomous neuropathy in patents with type 2 diabetes depended on diabetes duration,quality of carbohydrate metabolism compensation, levels of hyperinsulinemia and insulin resistance. Mean levels of Willebrand factors andinflammation markers in patents with type 2 diabetes and overt vegetative dysfunction were significantly higher than in diabetic patients withoutautonomous neuropathy. Correlation analysis revealed significant correlation of CRP and IL-6 levels with results of standard ECG tests. Conclusion. Results of the study demonstrate chronic inflammation in patents with type 2 diabetes and cardiovascular form of diabetic autonomousneuropathy. Increased level of inflammation markers and its relation to severity of vegetative disorders and endothelial dysfunction confirm the roleof inflammation in pathogenesis of nervous co-morbidity in patents with type 2 diabetes.

scholarly journals Effect of a fatty meal on inflammatory markers in healthy volunteers with a family history of type 2 diabetes

2011 ◽  
Vol 106 (3) ◽  
pp. 364-368 ◽  
Author(s):  
Stephanie Madec ◽  
Valentina Corretti ◽  
Eleonora Santini ◽  
Ele Ferrannini ◽  
Anna Solini
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Family History ◽  
Healthy Volunteers ◽  
Adhesion Molecule ◽  
Cellular Adhesion ◽  
Fatty Meal ◽  
Cellular Adhesion Molecule ◽  
History Of

A family history of type 2 diabetes (T2D) confers a high risk of developing the disease, independent of that due to other common risk factors. Postprandial state is a pro-inflammatory condition associated with a transiently impaired endothelial function; an increased oxidative stress is considered as a mediator of such effects in T2D. We evaluated the short-term effect of a lipid meal on markers of early vascular damage in subjects at risk of developing T2D. A total of thirty-two healthy volunteers, divided according to the presence (FHD+) or absence (FHD − ) of a family history of T2D, underwent a fatty meal test. We measured the monocyte mRNA expressions of IL-6, IL-8 and IL-1β, and IL-6, soluble CD40 ligand (sCD40L), vascular cellular adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1) and nitrotyrosine plasma concentrations at baseline and in the post-meal phase, relating them to the lipid profile and other biochemical parameters. The basal expression of the cytokines did not differ in FHD −  and FHD+ subjects; neither was it modified by the meal ingestion. IL-6 and sCD40L plasma levels, similar in the two groups in the fasting state, did not vary after the meal. VCAM-1 and ICAM-1 increased in FHD+ subjects but not in FHD −  subjects. Nitrotyrosine, similar between the FHD −  and FHD+ subjects at baseline, increased more in FHD+ subjects than in FHD −  subjects after the meal. In conclusion, the presence of a familial history of T2D confers an abnormal endothelial activation after an oral lipid meal, coupled with an increased oxidative stress, supporting the hypothesis of an early endothelial dysfunction already present in healthy individuals prone to develop T2D.

Opposite relationship between circulating soluble CD14 concentration and endothelial function in diabetic and nondiabetic subjects

2005 ◽  
Vol 94 (09) ◽  
pp. 615-619 ◽  
Author(s):  
Abel López-Bermejo ◽  
Antoni Castro ◽  
Montserrat Broch ◽  
Georgina Peñarroja ◽  
Joan Vendrell ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endothelial Dysfunction ◽  
Cyclic Gmp ◽  
Diabetic Patients ◽  
C Reactive Protein ◽  
Type 2 Diabetic Patients ◽  
Soluble Cd14 ◽  
Reactive Protein ◽  
Type 2 Diabetic

SummaryRecent prospective studies indicate endothelial dysfunction and increased risk for cardiovascular events in patients with serological evidence of multiple infections. Soluble CD14 (sCD14) plays a key role in the neutralization of lipopolysaccharide (LPS), a well-established bacterial product inducing endothelial dysfunction. Insulin resistance was recently identified as a significant factor influencing circulating sCD14 concentration. Thus, we investigated the association of circulating sCD14 and endothelial dysfunction in subjects with well-established insulin resistance (patients with type 2 diabetes, n=40) compared to control nondiabetic subjects (n=100). To further explore the underlying mechanisms, we also analysed C-reactive protein and circulating NO2-/NO3- and cyclic GMP in the diabetic group. Serum sCD14 concentration (ELISA) was found to be differently associated with endothelium-dependent vasodilatation (EDVD, high-resolution ultrasound) in diabetic and non-diabetic subjects. In nondiabetic subjects, serum sCD14 and C-reactive protein correlated negatively with EDVD (r= −0.21, p=0.03, and r=−0.21, p=0.03, respectively). In a partial correlation analysis, these associations remained significant after controlling for age and weight (sCD14 and EDVD, r=−0.23, p=0.023; C-reactive protein and EDVD, r=−0.21, p=0.03; sCD14 and C-reactive protein, r=0.30, p=0.002). In contrast, sCD14 was positively associated with EDVD in type 2 diabetic patients (r= 0.37, p=0.019,). Interestingly, sCD14 was also associated with NO2-/NO3- in this group (r=0.62, p=0.001, n=22). EDVD also correlated with cyclic GMP (r=0.47, p=0.03, n=22). In summary, circulating sCD14 is associated with endothelial function. While in non-diabetic subjects sCD14 behaves as an acute phase reactant, its role in type 2 diabetic patients should be further clarified. These findings need to be confirmed in further studies with larger number of patients.

High Levels of Adhesion Molecules Are Associated with Impaired Endothelium-dependent Vasodilation in Patients with Peripheral Arterial Disease

2001 ◽  
Vol 85 (01) ◽  
pp. 63-66 ◽  
Author(s):  
Vincenzo Martone ◽  
Tiziana de Cristofaro ◽  
Salvatore Corrado ◽  
Antonio Silvestro ◽  
Anna Maria Di Donato ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Close Association ◽  
Plasma Concentrations ◽  
Arterial Disease ◽  
Cellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Cellular Adhesion Molecule

SummarySoluble intercellular adhesion molecule-1 (sICAM-1) and vascular cellular adhesion molecule-1 (sVCAM-1) were measured alongside flow-mediated vasodilation (FMD) in 34 patients with intermittent claudication and 14 control subjects. Patients with plasma sICAM-1 >253 ng/mL (median value) showed lower FMD than those with sICAM-1 <253 ng/mL (5.6 ± 1.8% vs 9.6 ± 4.2%, p <0.01). Similarly, in the 17 patients with plasma sVCAM-1 >414 ng/mL, FMD was lower than in the remaining 17 patients (6.1 ± 1.9% vs 9.2 ± 4.5%, p <0.05). Additionally, when endothelial dysfunction was defined as FMD ≤5.5%, patients with FMD below this value had higher plasma concentrations of sICAM-1 and sVCAM-1 than those with FMD >5.5%. Therefore, our findings indicate a close association between elevated plasma levels of adhesion molecules and endothelial dysfunction. As impaired endothelial function is one of the first steps in atherogenesis, our findings have clinical relevance since they serve as the basis for further evaluation of sICAM-1 and sVCAM-1 as potential plasma markers for progression of atherosclerosis in a population at high risk.

scholarly journals Weight reduction ameliorates inflammatory cytokines, adipocytokines and endothelial dysfunction biomarkers among Saudi patients with type 2 diabetes

2020 ◽  
Vol 20 (3) ◽  
pp. 1329-1336
Author(s):  
Shehab M Abd El-Kader ◽  
Osama H Al-Jiffri ◽  
Ziyad A Neamatallah ◽  
Afnan M AlKhateeb ◽  
Saad S AlFawaz
Keyword(s):  
Type 2 Diabetes ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Inflammatory Cytokines ◽  
Adhesion Molecule ◽  
Weight Reduction ◽  
Control Group ◽  
Cellular Adhesion Molecule ◽  
The Impact

Background: Type 2 diabetes mellitus (T2DM) considered as one of the cardiovascular disorders (CVD) principle risk fac- tor as diabetes is associated with abnormal levels of endothelial function, inflammatory and adipocytokines. Objective: The aim of this study was to measure the impact of weight reducing on inflammatory cytokines, adipocytokines and endothelial function biomarkers among obese T2DM patients. Methods: One–hundred T2DM patients enrolled in the present study; the age range was 35-55 year. Participants shared in this study were enrolled in group (A) received diet control and aerobic exercise on treadmill, while, group (B) had no inter- vention for 3 months. Results: The mean values of body mass index (BMI), tumor necrosis factor –alpha (TNF-α), interleukin-6 (IL-6), leptin, inter-cellular adhesion molecule (ICAM-1) ,vascular cell adhesion molecule (VCAM-1), E-selectin and plasminogen activator inhibitor-1 activity (PAI-1 activity) were significantly decreased and adiponectin was increased significantly in the training group, however the results of the control group were not significant. Also, there were significant differences between both groups at the end of the study. Conclusion: Weight reducing program modulates inflammatory cytokines, adipocytokines and endothelial function bio- markers among obese T2DM patients. Keywords: Diabetes; endothelial dysfunction biomarkers; cytokines; adipocytokines; weight reduction.

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