scholarly journals NO (Nitric Oxide) to Type 2 Diabetes Induced Endothelial Dysfunction: Crosstalk with ET-1 (Endothelin-1)

2017 ◽  
Vol 2 (1) ◽  
Author(s):  
Omanwar Swati
Keyword(s):  
Nitric Oxide ◽  
Type 2 Diabetes ◽  
Endothelial Dysfunction ◽  
Endothelin 1

scholarly journals Obesity, type 2 diabetes, and impaired insulin-stimulated blood flow: role of skeletal muscle NO synthase and endothelin-1

2017 ◽  
Vol 122 (1) ◽  
pp. 38-47 ◽  
Author(s):  
Leryn J. Reynolds ◽  
Daniel P. Credeur ◽  
Camila Manrique ◽  
Jaume Padilla ◽  
Paul J. Fadel ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Vastus Lateralis ◽  
Glucose Disposal ◽  
Endothelin 1 ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Increased endothelin-1 (ET-1) and reduced endothelial nitric oxide phosphorylation (peNOS) are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), but studies examining these links in humans are limited. We sought to assess basal and insulin-stimulated endothelial signaling proteins (ET-1 and peNOS) in skeletal muscle from T2D patients. Ten obese T2D [glucose disposal rate (GDR): 6.6 ± 1.6 mg·kg lean body mass (LBM)−1·min−1] and 11 lean insulin-sensitive subjects (Lean GDR: 12.9 ± 1.2 mg·kg LBM−1·min−1) underwent a hyperinsulinemic-euglycemic clamp with vastus lateralis biopsies taken before and 60 min into the clamp. Basal biopsies were also taken in 11 medication-naïve, obese, non-T2D subjects. ET-1, peNOS (Ser1177), and eNOS protein and mRNA were measured from skeletal muscle samples containing native microvessels. Femoral artery blood flow was assessed by duplex Doppler ultrasound. Insulin-stimulated blood flow was reduced in obese T2D (Lean: +50.7 ± 6.5% baseline, T2D: +20.8 ± 5.2% baseline, P < 0.05). peNOS/eNOS content was higher in Lean under basal conditions and, although not increased by insulin, remained higher in Lean during the insulin clamp than in obese T2D ( P < 0.05). ET-1 mRNA and peptide were 2.25 ± 0.50- and 1.52 ± 0.11-fold higher in obese T2D compared with Lean at baseline, and ET-1 peptide remained 2.02 ± 1.9-fold elevated in obese T2D after insulin infusion ( P < 0.05) but did not increase with insulin in either group ( P > 0.05). Obese non-T2D subjects tended to also display elevated basal ET-1 ( P = 0.06). In summary, higher basal skeletal muscle expression of ET-1 and reduced peNOS/eNOS may contribute to a reduced insulin-stimulated leg blood flow response in obese T2D patients. NEW & NOTEWORTHY Although impairments in endothelial signaling are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), human studies examining these links are limited. We provide the first measures of nitric oxide synthase and endothelin-1 expression from skeletal muscle tissue containing native microvessels in individuals with and without T2D before and during insulin stimulation. Higher basal skeletal muscle expression of endothelin-1 and reduced endothelial nitric oxide phosphorylation (peNOS)/eNOS may contribute to reduced insulin-stimulated blood flow in obese T2D patients.

scholarly journals ASSESSMENT OF ENDOTHELIAL HEMOSTASIS; SERUM NITRIC OXIDE AND ENDOTHELIN-1 LEVELS IN ISCHEMIC CEREBROVASCULAR STROKE WITH OR WITHOUT TYPE 2 DIABETES.

2017 ◽  
Vol 5 (3) ◽  
pp. 1391-1399
Author(s):  
NearmeenM. Rashad ◽  
◽  
NeveenG. Elantouny ◽  
AmlS.El Shal ◽  
HalaA. Fathy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Type 2 Diabetes ◽  
Endothelin 1 ◽  
Cerebrovascular Stroke

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 Effect of oxidative stress on endothelium in patients with heart failure and type 2 diabetes ­mellitus

2020 ◽  
Vol 101 (1) ◽  
pp. 13-17
Author(s):  
F I Mammadova
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Chronic Heart Failure ◽  
Endothelial Dysfunction ◽  
Control Group

Aim. To estimate the severity of endothelial dysfunction and effects of nitric oxide, thiol status and cystatin on the progression of chronic heart failure and chronic heart failure in type 2 diabetes mellitus. Methods. 80 patients (men and women) with chronic heart failure were included. All patients were divided into two groups: the first group 39 patients with chronic heart failure, the second 41 people with chronic heart failure and type 2 diabetes mellitus. The control group consists of 20 healthy donors. To obtain statistically significant differences with the control group the minimum sample size for observations was determined based on the target variance of a small sample (n=10). The lipid profile and carbohydrate metabolism, endothelin-1, cystatin, nitric oxide were evaluated. Statistical processing was performed using Microsoft Office Excel and IBM SPSS Statistics 20 software. Results. Changes in lipid metabolism were found in both groups, while an increase in carbohydrate metabolism was observed in patients with chronic heart failure with type 2 diabetes mellitus. Under conditions of oxidative stress in patients with chronic heart failure, a decrease in the content of thiol status and an increase in the amount of nitric oxide in the blood serum were recorded. The endothelin-1 level was elevated, particularly in the second group, which indicates a more serious endothelial dysfunction with increased glucose content in patients with chronic heart failure. Conclusion. The level of cystatin C as an atherogenic risk factor was equally increased in the studied patients, possibly it affected by the rate of disease progression; feasible to use these markers to detect the progression of chronic heart failure in the early stages.

scholarly journals Endothelial dysfunction and diabetes

2005 ◽  
Vol 58 (9-10) ◽  
pp. 459-464 ◽  
Author(s):  
Edita Stokic ◽  
Mirjana Djeric ◽  
Djordje Radak
Keyword(s):  
Nitric Oxide ◽  
Type 2 Diabetes ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Enzyme Inhibitors ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Lipid Lowering ◽  
Converting Enzyme Inhibitors ◽  
Lipid Lowering Agents

Endothelial function and dysfunction During the past two decades, there has been an increasing recognition of the importance of normal endothelial function in the maintenance of vascular homeostasis and vascular health. Abnormalities in the function of endothelium have been recognized in a number of conditions. One of the most important abnormalities of endothelial dysfunction appears to be changes in the bioavailability of nitric oxide. It now appears clear that abnormalities in endothelial dysfunction are associated with abnormalities in the production of nitric oxide and/or abnormalities in the rate of its degradation. Either way, loss of the functional availability of nitric oxide appears to be an important characteristic of endothelial dysfunction. Endothetial dysfunction and diabetes lmpaired endothcliul-dependent vasodilatation has been described in patients with type 1 and type 2 diabetes, and the degree of impairment may correlate with glycemic control Hyperglycemia itself appears to affect multiple mechanisms that increase atherosclerosis. Hyperglycemia enhances oxidation, thrombosis, inflammation, matrix production, and the formation of advanced glycation end-products and other metabolites that can potentially damage the vasculature. Treatment of endothelial dysfunction A number of trials have demonstrated that therapy with lipid lowering agents (statins) as well as angiotensin converting enzyme inhibitors is associated with improvements in endothelial function in diabetes. These agents have also been shown to improve prognosis in patients with a number of underlying cardiac diseases and risk factors for cardiac disease. Therefore, it seems that interventions that lead to improvement in endothelial function can be associated with improvements in cardiovascular outcome. The role of antioxidant therapy is controversial. No data have been published regarding the effects of hormonal replacement therapy on endothelial dysfunction in postmenopausal women with type 2 diabetes.

scholarly journals P0978THE EFFECTS OF CHRONIC DAPAGLIFLOZIN TREATMENT ON THE RENAL MICROVASCULATURE IN A RAT MODEL OF TYPE 2 DIABETES

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Connie Ow ◽  
Vijayakumar Sukumaran ◽  
Jennifer Ngo ◽  
Cheng Kun Du ◽  
Akihiro Fujiwara ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Endothelial Dysfunction ◽  
Rat Model ◽  
Renal Injury ◽  
Diabetic Rats ◽  
Renal Microvasculature ◽  
Vasodilatory Function

Abstract Background and Aims Chronic kidney disease (CKD) is an ever-growing concern and CKD associated with diabetes accounted for ∼ 35% of new cases of end-stage renal failure. Clinical trials with insulin-independent sodium-glucose co-transporter 2 (SGLT2) inhibitors not only showed significant improvements in hyperglycemia and thus renal damage, but also reduced the risk of adverse cardiovascular events. Microvessels supply local tissue oxygen demands and are important controllers of regional perfusion. Endothelial dysfunction has been posited to be an important factor driving the pathogenesis of diabetic nephropathy, largely through impaired eNOS activity and thus reduced nitric oxide bioavailability. Thus, we aim to determine the effects of SGLT2 inhibition on vasodilator function in the renal vasculature. We hypothesize that rats chronically treated with dapagliflozin, a SGLT2 inhibitor, improves renal endothelial function and the microvessels are better able to maintain perfusion in response to the inhibition of nitric oxide synthase and prostaglandin blockade. Method Male Zucker fatty diabetic rats (8 wk old), a model of type 2 diabetes, were given daily oral gavage of 1 mg/kg dapagliflozin or its vehicle for up to 22 wks of age (n=6/group). Renal excretory function, glomerular filtration rate (GFR) and indices of renal injury was assessed before treatment and after every 4 wks up until 22 wks of age. GFR was assessed via transcutaneous clearance of FITC-sinistrin. Vasodilator function of the renal microvasculature was assessed via X-ray microangiography. We conducted successive imaging of the microvessels before and during infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) which facilitated the assessment of endothelium dependent and independent dilation respectively. After which, rats were given successive boluses of L-NAME and indomethacin to assess the vasodilatory function of the microvasculature independent of nitric oxide and prostaglandins respectively. These inhibitors were given under the conditions of SNP clamp which allowed for us to titrate the blood pressure to baseline levels. Lastly, we assessed the ability of endothelium hyperpolarizing factors (EDHFs) to maintain microvascular perfusion when SNP infusion ceased and an infusion of ACh commenced while still under the effects of L-NAME and indomethacin. Results As expected, dapagliflozin alleviated hyperglycemia across the treatment period. There was a tendency for dapagliflozin to ameliorate the decline of GFR, although this apparent effect was not statistically significant. Dapagliflozin did not appear to improve indices of renal injury. Treatment with dapagliflozin alleviated polyuria but did not appear to have an impact on urine osmolarity or sodium excretion. The responses (vessel diameter) of renal microvessels to ACh and SNP was greater in dapagliflozin than in vehicle fed rats. The microvessels of vehicle fed rats appeared to undergo relative constriction in response to L-NAME and indomethacin even under the effects of SNP clamp. In contrast, microvessels of dapagliflozin fed rats appeared to be relatively well-perfused after NOS and COX blockade. This suggests that dapagliflozin may improve endothelial dysfunction commonly associated with diabetic nephropathy. Following NOS and COX blockade, ACh was infused in rats to determine the status of vasodilatory function mediated by EDHFs. The microvessels in diabetic rats did not appear to be dilated after infusion of ACh, suggesting that vasodilatory effects of EDHFs on the vasculature is diminished in diabetic rats. Dapagliflozin appeared to improve this effect in that the renal microvessels were dilated even when NOS and COX production was blocked/inhibited. Conclusion Chronic treatment of dapagliflozin may improve endothelial dysfunction and thus retard the progression of diabetic nephropathy in a rat model of type 2 diabetes.

scholarly journals The effect of metformin treatment on the level of GLP-1, NT-proBNP and endothelin-1 in patients with type 2 diabetes mellitus

2021 ◽  
Vol 16 (8) ◽  
pp. 616-621
Author(s):  
L.K. Sokolova ◽  
Yu.B. Belchina ◽  
V.V. Pushkarev ◽  
S.A. Cherviakova ◽  
T.S. Vatseba ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Natriuretic Peptide ◽  
Enzyme Linked Immunosorbent Assay ◽  
Diabetic Patients ◽  
Metformin Treatment ◽  
Endothelin 1

Background. Type 2 diabetes mellitus (T2DM) is closely associated with an increased risk of cardiovascular diseases. It was shown that endothelial dysfunction is one of the key pathological events in the development of chronic vascular diabetic complications. An important effect of endothelial dysfunction is that it increases the production and biological activity of the potent vasoconstrictor and the pro-inflammatory peptide — endothelin (ET). Metformin is used in the treatment of T2DM as a first-line medication. It has been shown that the mechanism of action of metformin may be associated with biochemical processes in the gastrointestinal tract. Brain natriuretic peptide (BNP) is used as a marker in the diagnosis of heart failure. The purpose of this work was to determine and compare ET-1, NT-proBNP and glucagon-like peptide-1 (GLP-1) blood levels in diabetic patients treated with metformin. Materials and methods. NT-proBNP, GLP-1, endothelin-1 and glycated hemoglobin were determined using enzyme-linked immunosorbent assay. To compare the data groups, Student’s t-test and one-way ANOVA were used. Results. The content of ET-1 in the blood of patients with T2DM significantly exceeds its concentration in the control samples. Monotherapy with metformin leads to a decrease in ET-1 levels by more than 65 %. The combination therapy of metformin with insulin causes even greater decrease in ET-1. The blood level of GLP-1 in patients with T2DM is significantly, more than 2 times, reduced compared to healthy people. After metformin treatment, the content of GLP-1 is increased to the control level. The concentration of NT-proBNP in the blood of diabetic patients more than 2 times exceeds the control values. Treatment with metformin leads to a decrease in the content of natriuretic peptide by more than 40 %. Conclusions. Thus, treatment with metformin causes a decrease in ET-1 and NT-proBNP concentrations, and an increase in blood GLP-1 of patients with type 2 diabetes. These events together may indicate a positive protective effect of metformin on the cardiovascular system.

scholarly journals SEX DIFFERENCES OF ENDOTHELIAL DYSFUNCTION MARKERS — NITRIC OXIDE SYNTHASE AND HEME OXYGENASE IN RATS WITH 2 TYPE DIABETES MELLITUS

2018 ◽  
Vol 66 (4) ◽  
pp. 37-43
Author(s):  
Oleksii Borikov ◽  
Nataliia Gorbenko ◽  
Olha Ivanova ◽  
K. V. Taran ◽  
T. S. Litvinova ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Type 2 Diabetes ◽  
Endothelial Dysfunction ◽  
Nitric Oxide Synthase ◽  
Blood Vessels ◽  
Heme Oxygenase ◽  
Oxygenase Activity ◽  
Oxide Synthase ◽  
Nitric Oxide Synthase Activity

The effect of type 2 diabetes on the markers of endothelial dysfunction — nitric oxide synthase and heme oxygenase has been studied in rats, depending on sex. It was established that the activity of nitric oxide synthase in the blood vessels of female rats is significantly higher in comparison with males under physiological conditions. Type 2 diabetes leads to the different depression of the nitric oxide synthase activity in the blood vessels of females and males, which eliminates sexual differences in the activity of this enzyme. It was found that in contrast to nitric oxide synthase, the activity of heme oxygenase in vascular homogenate does not depend on the sex of intact animals. Type 2 diabetes leads to more expressive increase in heme oxygenase activity in female blood vessels compared to male rats. We can suppose that a more pronounced elevation of the heme oxygenase activity in case of a decrease the nitric oxide synthase activity is a compensatory mechanism for reducing of endothelial dysfunction in women with type 2 diabetes.

scholarly journals The pathogenetic significance of endothelial dysfunction in the development of diabetic nephropathy in patients with type 2 diabetes mellitus

2021 ◽  
Vol 2 (4) ◽  
pp. 65-72
Author(s):  
E. A. Reznikova ◽  
M. A. Gordeeva ◽  
A. R. Babaeva
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Endothelial Dysfunction ◽  
Healthy Individuals ◽  
Endothelin 1 ◽  
Circulating Markers ◽  
Von Willebrand ◽  
Dm Type 2 ◽  
Willebrand Factor

Objective: to determine the level of circulating markers of endothelial dysfunction (endothelin‑1, von Willebrand factor (vfV), endothelial NO-synthase (e‑NOS)) in the blood serum of patients with type 2 diabetes mellitus (DM), as well as to assess the pathogenetic significance endothelial dysfunction in the development of diabetic nephropathy.Materials and methods: the study included 93 patients with type 2 DM, including 28 men (30.1%) and 65 women (69.9%), aged 30 to 79 years, the average age of patients was 59.7±8.4 of the year. The main group included patients with both newly diagnosed type 2 DM and a long-term diabetic history. The duration of the disease averaged 9.5±7.5 years. The majority of patients with DM type 2 (92.5%) at the time of inclusion in the study had various variants of microvascular complications of diabetes, only a small number of patientsin this group (7.5%) had no signs of diabetic angiopathy. Signs of various stages of diabetic nephropathy were observed in 60 patients (69.2%). The comparison group consisted of 30 patients with essential arterial hypertension, including 12 men (40%) and 18 women (60%), aged 34 to 70 years, on average 56.1 ± 8.1 years. The control group consisted of 32 apparently healthy individuals. In all patients, along with routine methods of clinical, laboratory and instrumental examination, the level of circulating markers of endothelial dysfunction (endothelin‑1, von Willebrand factor (vWF), endothelial NO-synthase (e‑NOS)) in blood serum was measured using enzyme-linked immunosorbent assay (ELISA).Results: in patients with DM type 2 and diabetic nephropathy, a statistically significant increase in the concentration of circulating markers of endothelial dysfunction was revealed in comparison with hypertensive patients and healthy individuals. An increase in the level of endothelin‑1 relative to the borderline reference value was found in 73 (78.5±4.1%), vfV in 63 (67.7±4.8%) and e‑NOS in 65 (69.9±4.7%) of patients with DM type 2. In the groups of participants with hypertension and healthy individuals, endothelial imbalance was noted by us significantly less often than in patients with DM type 2, the levels of endothelin‑1 and vfV in people with hypertension were increased in more cases than in healthy individuals. It was noted that the levels of circulating markers of endothelial dysfunction increase with an increase in the duration of DM type 2, and also significantly increase under conditions of carbohydrate decompensation.Conclusion: the results obtained confirm the pathogenetic role of endothelial dysfunction in the development of diabetic nephropathy in patients with type 2 diabetes, increasing endothelial imbalance in persons with a long diabetic history and lack of compensation for carbohydrate metabolism.

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