State of endothelial function, lipid spectrum and features of coronary vessels structure of rats with obesity and insulin resistance under iodine deficiency conditions

The aim of the study was to investigate the changes of endothelin-1 content, blood lipid spectrum parameters, structural features of coronary vessels of rats with insulin resistance and obesity under conditions of adequate iodine supply and iodine deficiency. For the modeling of insulin resistance, rats were kept on high-fructose, obesity – high-calorie, iodine deficiency – iodine deficiency diets. It was found that the development of insulin resistance, obesity and iodine deficiency was accompanied by an increase of endothelin-1 level in 2.41, 2.31 times and at 80.17% in blood serum, relative to the data in intact animals. Insulin resistance and obesity under conditions of limited iodine supply leads to the significant changes in endothelial dysfunction (increase in the level of endothelin-1 in 3.02 and 2.50 times relative to control and at 67.38 and 39.40% – relative to mono iodine deficiency) and dyslipidemia (increase in the atherogenic factor at 48.08% – 4.20 times relative to isolated insulin resistance, obesity and iodine deficiency). Such changes were consistent with the structural violations. In insulin-resistant animals focal unevenness of the outer and inner contours, their uneven thickness, areas of homogeneous enlightenment were observed under the conditions of iodine deficiency in the arterioles and minor arteries of the myocardium. In obese animals under the conditions of iodine deficiency, the vessels of the microcirculatory bed were dilated and overflown with erythrocytes. Endotheliocytes with nuclei elongated along the wall, in some places there is a swelling of the cytoplasm of endotheliocytes. In the wall of minor arteries there are transparent vacuoles, areas of homogeneous eosinophilia, which are caused by the accumulation of glycoproteins. Thus, the development of insulin resistance and obesity in iodine deficiency is accompanied by more significant changes in endothelial function and an increase in proatherogenic fractions in the blood lipid spectrum, as evidenced by changes in the structural organization of myocardial vessels than with proper iodine supply.

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Adipokiny, insulinorezistentnost' i aktivnost' simpato-adrenalovoy sistemy u yunoshey s ozhireniem, manifestirovavshim v pubertatnyy period

Obesity and metabolism ◽

10.14341/omet2012249-52 ◽

2012 ◽

Vol 9 (2) ◽

pp. 49-52 ◽

Cited By ~ 3

Author(s):

A F Verbovoy ◽

E V Mitroshina ◽

Yu A Dolgih

Keyword(s):

Insulin Resistance ◽

Blood Pressure ◽

Young Men ◽

Blood Lipid ◽

The Other ◽

Control Group ◽

Normal Blood Pressure ◽

Sympathoadrenal System ◽

Increased Activity ◽

Lipid Spectrum

69 young men with obesity manifesting at puberty have been examined. The average age was 19,22±0,26. 17 healthy young men, whose average age was 22 ± 0,72 years old, constituted a control group. The examined were divided according to their blood pressure (BP): the first subgroup included 36 young men with normal blood pressure, the other subgroup included 33 young men with arterial hypertension. Levels of blood lipid spectrum, levels of leptin, resistin, adiponectin, insulin in serum, urinary metanephrine excretion were measured. We obtained the following results: young men with obesity identified atherogenic changes in lipid metabolism, insulin resistance and compensatory hyperinsulinemia. Regardless of the level of blood pressure they showed a significant increase in leptin levels. In the subgroup of patients with hypertension we found increased urinary excretion of metanephrine, indicating increased activity of the sympathoadrenal system and its involvement in the formation of hypertension. The level of adiponectin in the surveyed tended to decrease, more pronounced in the combination of obesity and hypertension.

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Abstract 297: Increased ETA Receptor-Mediated Contractility of Thoracic Aorta by Endothelin-1 in High-Fat-Diet--Fed Insulin-Resistant Rats

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.32.suppl_1.a297 ◽

2012 ◽

Vol 32 (suppl_1) ◽

Author(s):

Ramarao Poduri ◽

Payal Gupta ◽

Anil Gulati

Keyword(s):

Insulin Resistance ◽

Thoracic Aorta ◽

High Fat Diet ◽

Specific Binding ◽

Dependent Manner ◽

High Fat ◽

Contractile Responses ◽

Endothelin 1 ◽

Insulin Resistant ◽

Eta Receptor

Abstract: Increased incidences of cardio-vascular complications in diabetic conditions are a major concern. Endothelin-1 (ET-1) is an important regulator of vascular contractility, and its effects are mediated through ETA and ETB. Previous data from the lab indicates that GPCR mediate contractile responses are enhanced and the present study is aimed to extend the hypothesis that ETA receptor mediated contractile responses of ET-1 under insulin-resistant condition are enhanced. Methods: Male Sprague-Dawley (SD) rats were kept on high-fat diet (HFDIRR, 8 weeks) for inducing insulin-resistance. Further, b-cell specific toxin streptozotocin (STZ, 50 mg/kg; i.p.) was used to induce hypoinsulinemia in rats. The responses of ET-1, ACh, KCl and Ang -II were recorded in the concentration-dependent manner in the thoracic aorta of rats. Specific ETA receptor antagonist, BMS182874 was used to confirm the findings. Specific binding of [3H]-BQ123 was performed to determine the characteristics of ETA receptors. Biochemical parameters were measured and induction of insulin-resistance was confirmed by intra-peritoneal glucose tolerance test (IPGTT). Results: ET-1 mediated contractile response (4541 ± 274 mg/mm2 (mean ± s.e.m. (n=8)) was significantly higher in insulin-resistant rats, while that of KCl unchanged. Tempol (100μM) restored the ET-1 mediated contractions in HFDIRR (4541 ± 274 vs 3406 ± 252.8 mg/mm2; p < 0.001; (n=5)). BMS182874 restored NO-mediated endothelium-dependent ACh relaxation in HFDIRR. The specific binding of [3H]-BQ123 to ETA receptors (112.35 ± 5.19 vs. 39.74 ± 4.04 f mol/mg; P < 0.001; (n=5)) was increased in HFDIRR. Conclusions: Insulin-resistance up-regulates ETA receptor may be responsible enhanced ET-1 mediated contractility of the thoracic aorta.

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Chronic intermittent hypoxia accelerates coronary microcirculatory dysfunction in insulin-resistant Goto-Kakizaki rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00112.2016 ◽

2016 ◽

Vol 311 (2) ◽

pp. R426-R439 ◽

Cited By ~ 9

Author(s):

Yi Ching Chen ◽

Tadakatsu Inagaki ◽

Yutaka Fujii ◽

Daryl O. Schwenke ◽

Hirotsugu Tsuchimochi ◽

...

Keyword(s):

Insulin Resistance ◽

Endothelial Function ◽

Intermittent Hypoxia ◽

Wistar Rats ◽

Chronic Intermittent Hypoxia ◽

Vascular Endothelial ◽

Gk Rats ◽

Insulin Resistant ◽

Coronary Endothelial Function

Chronic intermittent hypoxia (IH) induces oxidative stress and inflammation, which impair vascular endothelial function. Long-term insulin resistance also leads to endothelial dysfunction. We determined, in vivo, whether the effects of chronic IH and insulin resistance on endothelial function augment each other. Male 12-wk-old Goto-Kakizaki (GK) and Wistar control rats were subjected to normoxia or chronic IH (90-s N2, 5% O2 at nadir, 90-s air, 20 cycles/h, 8 h/day) for 4 wk. Coronary endothelial function was assessed using microangiography with synchrotron radiation. Imaging was performed at baseline, during infusion of acetylcholine (ACh, 5 μg·kg−1·min−1) and then sodium nitroprusside (SNP, 5 μg·kg−1·min−1), after blockade of both nitric oxide (NO) synthase (NOS) with Nω-nitro-l-arginine methyl ester (l-NAME, 50 mg/kg) and cyclooxygenase (COX, meclofenamate, 3 mg/kg), and during subsequent ACh. In GK rats, coronary vasodilatation in response to ACh and SNP was blunted compared with Wistar rats, and responses to ACh were abolished after blockade. In Wistar rats, IH blunted the ability of ACh or SNP to increase the number of visible vessels. In GK rats exposed to IH, neither ACh nor SNP were able to increase visible vessel number or caliber, and blockade resulted in marked vasoconstriction. Our findings indicate that IH augments the deleterious effects of insulin resistance on coronary endothelial function. They appear to increase the dependence of the coronary microcirculation on NO and/or vasodilator prostanoids, and greatly blunt the residual vasodilation in response to ACh after blockade of NOS/COX, presumably mediated by endothelium-derived hyperpolarizing factors.

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Postprandial endothelial function does not differ in women by race: an insulin resistance paradox?

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00434.2011 ◽

2012 ◽

Vol 302 (2) ◽

pp. E218-E225 ◽

Cited By ~ 5

Author(s):

Ranganath Muniyappa ◽

Vandana Sachdev ◽

Stanislav Sidenko ◽

Madia Ricks ◽

Darleen C. Castillo ◽

...

Keyword(s):

Insulin Resistance ◽

African American ◽

Insulin Sensitivity ◽

Endothelial Function ◽

African American Women ◽

Racial Differences ◽

White Women ◽

Sensitivity Index ◽

American Women ◽

Insulin Resistant

Insulin resistance is associated with endothelial dysfunction. Because African-American women are more insulin-resistant than white women, it is assumed that African-American women have impaired endothelial function. However, racial differences in postprandial endothelial function have not been examined. In this study, we test the hypothesis that African-American women have impaired postprandial endothelial function compared with white women. Postprandial endothelial function following a breakfast (20% protein, 40% fat, and 40% carbohydrate) was evaluated in 36 (18 African-American women, 18 white women) age- and body mass index (BMI)-matched (age: 37 ± 11 yr; BMI: 30 ± 6 kg/m2) women. Endothelial function, defined by percent change in brachial artery flow-mediated dilation (FMD), was measured at 0, 2, 4, and 6 h following a meal. There were no significant differences between the groups in baseline FMD, total body fat, abdominal visceral fat, and fasting levels of glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, or serum estradiol. Although African-American women were less insulin-sensitive [insulin sensitivity index (mean ± SD): 3.6 ± 1.5 vs. 5.2 ± 2.6, P = 0.02], both fasting triglyceride (TG: 56 ± 37 vs. 97 ± 49 mg/dl, P = 0.007) and incremental TG area under the curve (AUC0–6hr: 279 ± 190 vs. 492 ± 255 mg·dl−1·min−1·10−2, P = 0.008) were lower in African-American than white women. Breakfast was associated with a significant increase in FMD in whites and African-Americans, and there was no significant difference in postprandial FMD between the groups ( P > 0.1 for group × time interactions). Despite being insulin-resistant, postprandial endothelial function in African-American women was comparable to white women. These results imply that insulin sensitivity may not be an important determinant of racial differences in endothelial function.

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Insulin impairs endothelium-dependent vasodilation independent of insulin sensitivity or lipid profile

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00539.2003 ◽

2004 ◽

Vol 286 (1) ◽

pp. H76-H82 ◽

Cited By ~ 29

Author(s):

Umberto Campia ◽

Gail Sullivan ◽

Melissa B. Bryant ◽

Myron A. Waclawiw ◽

Michael J. Quon ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Endothelial Function ◽

Lipid Profile ◽

Vascular Function ◽

Sensitivity Index ◽

High Cholesterol ◽

Insulin Resistant ◽

Normotensive Subjects ◽

Dependent Flow

Insulin resistance is a risk factor for atherosclerosis and is associated with hyperinsulinemia, abnormal lipid profile, and hypertension. Whether hyperinsulinemia affects vascular function independent of insulin resistance or other metabolic risk factors is unknown. This investigation aimed to assess the effects of hyperinsulinemia on endothelial function in subjects with a spectrum of insulin sensitivity and lipid profile. Endothelium-dependent (flow-mediated dilation, FMD) and -independent (nitroglycerin) responses of the brachial artery were studied by high-resolution ultrasound before and during hyperinsulinemia (euglycemic clamp) in 25 normoglycemic, normotensive subjects. Participants were divided into an insulin-sensitive and an insulin-resistant subgroup based on their sensitivity index values, with a cutoff of 8, and into a normal-cholesterol and a high-cholesterol subgroup based on their total cholesterol levels, with a cutoff of 5.2 mmol/l (200 mg/dl). In the whole population, FMD was lower during hyperinsulinemia compared with baseline (2.3 ± 0.6% vs. 6 ± 0.6%; P < 0.001). Resting FMD was lower in the insulin-resistant subgroup compared with the insulin-sensitive subgroup (4.2 ± 0.9% vs. 7.4 ± 0.8%; P = 0.014) and in the high-cholesterol subjects compared with the normal-cholesterol subjects (4.4 ± 0.7% vs. 8 ± 0.7%; P = 0.002). Hyperinsulinemia decreased FMD in both the insulin-sensitive (from 7.4 ± 0.8% to 3.6 ± 0.4%; P < 0.001) and insulin-resistant (from 4.2% to 1.22%; P = 0.012) subgroups and in both the normal-cholesterol (from 8 ± 0.7% to 3.9 ± 0.4%; P < 0.001) and high-cholesterol (from 4.4 ± 0.7% to 1.1 ± 0.8%; P = 0.01) participants. Acute hyperinsulinemia impairs conduit vessel endothelial function independent of insulin sensitivity and lipid profile. Insulin may trigger endothelial dysfunction and promote atherosclerosis.

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