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Biomedical subjects

Shinichiro Ueda

Publications and source records attributed to Shinichiro Ueda.

8 recordsLinked to original sources
PubMed2006

A novel index of insulin resistance determined from the homeostasis model assessment index and adiponectin levels in Japanese subjects.

Insulin resistance is the principal cause of glucose intolerance and type 2 diabetes and induces progression of severe atherosclerosis in these patients. Adiponectin, the adipose-specific proteins, is known to correlate negatively with insulin resistance in patients with obesity and type 2 diabetes. The purpose of this study was to evaluate the potential of using serum adiponectin levels as a marker of insulin resistance in various states of insulin resistance. Furthermore, we attempted to establish a modified index of the homeostasis model assessment index (HOMA-IR), calculated from the product of serum insulin and plasma glucose levels divided by serum adiponectin levels (HOMA-AD). We recruited 117 Japanese subjects with various degrees of glucose tolerance and determined serum adiponectin levels and insulin sensitivity (M-value) by using the euglycemic hyperinsulinemic clamp technique. M-value, the gold standard index of insulin resistance, correlates significantly and independently with fasting insulin (r=-0.313, P<0.001), glucose (r=-0.319, P<0.001), and adiponectin (r=0.241, P<0.002) levels. M-values were more significantly correlated with HOMA-AD (r=-0.643, P<0.001) than HOMA-IR values (r=-0.591, P<0.001). In subjects with moderate hyperglycemia (fasting glucose levels>8.0mmol/L, n=30), HOMA-AD showed a more significant correlation with the M-value than HOMA-IR (r=-0.535, P=0.005 versus r=-0.461, P=0.010). We would therefore like to propose a novel index, HOMA-AD, as a simple and adequate index for determining insulin resistance even in diabetic patients with overt hyperglycemia.

Adiponectin↗
PubMed2006

Vascular lipotoxicity: endothelial dysfunction via fatty-acid-induced reactive oxygen species overproduction in obese Zucker diabetic fatty rats.

Vascular endothelial dysfunction has been demonstrated in obesity, but the molecular basis for this link has not been clarified. We examined the role of free fatty acids (FFA) on vascular reactivity in the obese fa/fa Zucker diabetic fatty (ZDF) rat. Addition of acetylcholine produced a dose-dependent relaxation in aortic rings of ZDF and lean +/+ rats, but the ED(50) value was higher in ZDF (-6.80 +/- 0.05 vs. -7.11 +/- 0.05 log(10) mol/liter, P = 0.033). A 2-wk treatment with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, pitavastatin (3 mg/kg/d) or a reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, apocynin (5 mmol/liter in drinking water), improved the response in ZDF (ED(50), -7.16 +/- 0.03 and -7.14 +/- 0.05 log(10) mol/liter, P = 0.008 and P = 0.015 vs. vehicle, respectively). Vasodilator response to sodium nitroprusside was identical between ZDF and +/+ rats. Vascular reactive oxygen species (ROS) levels and NADPH oxidase activity in aorta were increased in ZDF rats but were decreased by pitavastatin. In in vitro cell culture, intracellular ROS signal and NADPH oxidase subunit mRNA were increased by palmitate, but this palmitate-induced ROS production was inhibited by NADPH oxidase inhibitor or pitavastatin. In conclusion, FFA-induced NADPH oxidase subunit overexpression and ROS production could be involved in the endothelial dysfunction seen in obese ZDF rats, and this could be protected by pitavastatin or NADPH oxidase inhibitors.

Acetophenones↗
PubMed2006

What we learnt from randomized clinical trials and cohort studies of antioxidant vitamin? Focus on vitamin E and cardiovascular disease.

There is no doubt that oxidative stress is pivotally involved in the process of atherosclerosis. Thus antioxidants, particularly vitamin E, have been expected to retard the development of atherosclerosis. In fact, several cohort studies suggested reduced cardiovascular risk in persons taking vitamin E supplements. However, randomized clinical trials of vitamin E did not show any benefit of vitamin E supplementation in terms of prevention of coronary heart disease and death. Discrepancy between cohort studies and randomized clinical trials may be partly explained by difference in coronary risk in study participant. However, use of vitamin E supplementation in low risk population has not been justified yet.

Antioxidants↗
PubMed2005

Inhibition of the renin-angiotensin system prevents free fatty acid-induced acute endothelial dysfunction in humans.

OBJECTIVE: An elevated free fatty acid (FFA) level impairs endothelium-dependent vasodilation in humans, which may be pathophysiologically relevant to the development of endothelial dysfunction in patients with insulin resistance. We investigated the effect of inhibition of the renin-angiotensin system (RAS) on FFA-induced endothelial dysfunction. METHODS AND RESULTS: Changes in forearm blood flow during intra-arterial infusion of acetylcholine were measured by plethysmography before and after systemic infusion of lipid/heparin in 10 healthy subjects given a single dose of placebo, losartan (50 mg), or perindopril (8 mg). Endothelial function after lipid/heparin infusion was also investigated with the coinfusion of vitamin C or NG-monomethyl-L-arginine (L-NMMA). Elevated FFA significantly reduced the response to acetylcholine by 37.7% (P=0.0096) without L-NMMA, but not the response with L-NMMA, whereas FFA did not affect the response to nitroprusside. The single dose of either losartan or perindopril completely prevented FFA-induced endothelial dysfunction. Vitamin C also prevented FFA-induced endothelial dysfunction. CONCLUSIONS: Elevated FFA levels by lipid/heparin infusion, which may partly mimic the abnormal lipid profile in patients with insulin resistance, caused endothelial dysfunction via RAS activation and the presumably resultant oxidative stress in humans. Our results suggest the therapeutic rationale for RAS inhibition in patients with high FFA levels.

Acetylcholine↗
PubMed2004

Methodological validity and feasibility of the nitric oxide clamp technique for nitric oxide research in human resistant vessels.

N(G)-methyl-L-arginine (L-NMMA) has been widely used for nitric oxide (NO) research, particularly for the assessment of NO-dependent vasodilatation evoked by agonists. However, such experiments may not be straightforward because L-NMMA causes vasoconstriction, which itself must non-specifically affect responses to any vasoactive agents. Therefore, in order to more accurately estimate the roles of NO in human vessels in vivo, we developed an NO clamp technique that uses co-infusion of an NO donor with L-NMMA. To assess the validity and feasibility of this technique, we compared the effects of intra-arterial infusion of L-NMMA on the forearm blood flow responses to vasodilators with and without the NO clamp technique in healthy males. All drugs were intra-arterially infused and changes in forearm blood flow (FBF) were measured by strain-gauge plethysmography. Vasodilatation evoked by atrial natriuretic peptide was significantly attenuated by L-NMMA alone (p = 0.001) but not by the NO clamp technique. L-NMMA significantly attenuated the responses to acetylcholine either with or without the NO clamp technique. However, the ratio of the area under the curve (AUC) of acetylcholine with L-NMMA to that without L-NMMA was significantly higher when the NO clamp technique was not used (AUC ratio: 0.62 +/- 0.13 vs. 0.48 +/- 0.14, respectively; p = 0.031). The contribution of NO to the FBF responses to vasodilators may be more properly assessed by the co-infusion of L-NMMA with the NO clamp technique than by L-NMMA alone. Our NO clamp technique thus appears to be valid and feasible for human NO research.

Acetylcholine↗
PubMed2003

Hypoadiponectinemia is closely linked to endothelial dysfunction in man.

Vascular endothelial dysfunction has been demonstrated in overweight or obese patients, but the molecular basis for this link has not been clarified. We asked what the relationship was between adiponectin, an adipose-specific molecule, and endothelial function. Forearm blood flow (FBF) was measured during reactive hyperemia by using strain-gauge plethysmography in 76 Japanese subjects without a history of cardiovascular or cerebrovascular disease, diabetes mellitus, hepatic, or renal disease. The peak FBF and total reactive hyperemic flow [flow debt repayment (FDR)] during reactive hyperemia were correlated with waist circumference (r = -0.418 and -0.414, respectively) and body mass index (r = -0.597 and -0.626, respectively). After correcting for age, gender, and body mass index, the peak FBF was correlated with systolic blood pressure (r = -0.294; P = 0.010), free fatty acid (FFA) (r = -0.331; P = 0.004), and adiponectin in log 10 (r = 0.492; P < 0.001), and FDR was correlated with adiponectin in log 10 (r = 0.462; P = 0.001). In stepwise multiple regression analyses, predictive variables for peak FBF were adiponectin in log 10 (r = 0.468) and FFA (r = -0.292; r(2) = 0.487; P < 0.0001); and predictive variables for FDR were adiponectin in log 10 (r = 0.474) and FFA (r = -0.275; r(2) = 0.346, P < 0.0001). Endothelial function was impaired in proportion to the severity of obesity, and the level of severity was closely related to plasma adiponectin levels. Adiponectin may play a protective role against the atherosclerotic vascular change, and loss of effects enhances endothelial dysfunction, as in obese people.

Adiponectin↗
PubMed2002

Angiotensin II attenuates the vasodilating effect of a nitric oxide donor, glyceryl trinitrate: roles of superoxide and angiotensin II type 1 receptors.

OBJECTIVE: The development of tolerance to organic nitrates limits their usefulness in the treatment of heart disease. Activation of the renin-angiotensin system by heart failure itself and by nitrate therapy may be one possible mechanism underlying nitrate tolerance. We investigated the effect of subpressor doses of angiotensin II on the vasodilating effect of glyceryl trinitrate in human forearm resistance vessels of healthy male subjects by using venous occlusion strain-gauge plethysmography. METHODS: Glyceryl trinitrate was infused intra-arterially with angiotensin II or vehicle. The effect of blockade of angiotensin II type 1 receptors by candesartan or an antioxidant, vitamin C, on the interaction between angiotensin II and glyceryl trinitrate was also investigated. RESULTS: Angiotensin II infused at 5 pmol/min significantly attenuated the vasodilating effect of glyceryl trinitrate (mean +/- standard deviation [SD] of percentage change in forearm blood flow [FBF]: 28% +/- 20%, 79% +/- 59%, and 208% +/- 72% at 100, 250, and 1000 ng/min of glyceryl trinitrate with placebo; 8% +/- 18%, 47% +/- 41%, and 173% +/- 98% with angiotensin II at 1 pmol/min; and 2% +/- 27%, 39% +/- 40%, and 132% +/- 74% with angiotension II at 5 pmo;/min; P =.0259). Either a single dose of candesartan or coinfusion with vitamin C abolished the angiotensin II-induced attenuation of vasodilation of glyceryl trinitrate. CONCLUSION: Our results suggest that angiotensin II may attenuate the arterial vasodilating effect of glyceryl trinitrate through angiotensin type 1 receptors and presumably through receptor-mediated superoxide production, which may be relevant to the development of nitrate tolerance.

Adult↗