Biomedical subjects

Nobuyuki Ura

Publications and source records attributed to Nobuyuki Ura.

42 records · Page 3Linked to original sources

PubMed2003

Role of adiponectin in insulin-resistant hypertension and atherosclerosis.

Insulin resistance is one of the major risk factors associated with development of hypertension and atherosclerosis. Recent studies have shown that adiponectin, an adipocyte-derived hormone, may be involved in insulin resistance and development of atherosclerosis in diabetes patients. The aim of this study was to examine adiponectin levels in patients with essential hypertension to determine the relationships between adiponectin levels and insulin sensitivity and to examine the relationship of adiponectin with pulse wave velocity (PWV) in a general population based on the results of an epidemiological survey in Japan. In a clinical study, 20 normotensives (NT) and 30 non-treated essential hypertensives (EHT) were hospitalized, and euglycemic hyperinsulinemic glucose clamp (GC) was performed to evaluate insulin sensitivity defined as M value. EHT were divided into insulin-resistant EHT (EHT-R) and insulin-nonresistant EHT (EHT-N) according to the mean -1 SD of the M value of NT as a cut-off point. Fasting plasma glucose (FPG), immunoreactive insulin (IRI), and adiponectin concentrations were measured. There were no significant differences in body mass index (BMI) or FPG among the NT, EHT-N, and EHT-R groups. The M value and adiponectin concentration in EHT-R were significantly lower than those in the NT or EHT-N. The IRI level in the EHT-R was significantly higher than those in the other groups. A positive correlation between adiponectin concentration and M value was found in all subjects, and adiponectin concentration and M value were found to be significant determinants of each other in multiple regression analysis. In an epidemiological study, we studied 391 male inhabitants of rural communities in Hokkaido, Japan. Systolic blood pressure (SBP), BMI, FPG, IRI, and adiponectin were measured in all subjects early in the morning. Homeostasis model assessment (HOMA) values were calculated as an index of insulin sensitivity, and PWV was used as an index of atherosclerosis. A negative correlation between HOMA values and adiponectin concentration was found in all of the subjects. Multiple regression analysis revealed that adiponectin was a significant determinant for PWV in subjects less than 70 years of age. The results of the clinical study indicate that EHT-R had not only hyperinsulinemia but also a low concentration of adiponectin. The results of multiple regression analysis for determinants of degree of PWV using data obtained in the epidemiological study suggest that adiponectin plays a role in antiatherosclerosis, partly through improvement of insulin resistance.

Adiponectin↗

PubMed2003

Insulin sensitivity and lipid metabolism in human CD36 deficiency.

OBJECTIVE: CD36 has been proposed as a fatty acid translocase and a receptor for HDL and oxidized LDL. The association between CD36 deficiency and insulin resistance remains controversial. We investigated glucose and lipid metabolism in human CD36 deficiency. RESEARCH DESIGN AND METHODS: A total of 61 type I CD36-deficient patients and 25 control subjects were examined. Diabetes was defined as fasting glucose level > or =7 mmol/l or use of hypoglycemic agents. A homeostasis model assessment (HOMA) index was evaluated in patients without diabetes. Insulin resistance was defined as a HOMA index > or =1.73 (sensitivity 64.3%, specificity 78.9%; J Japan Diab Soc, 2000). RESULTS: Diabetes was identified in 12 (20%) of the 61 CD36-deficient patients. Fasting glucose, HbA(1c), and total cholesterol levels in the diabetic CD36-deficient patients were significantly higher than in the control subjects and the nondiabetic CD36-deficient patients. Regardless of diabetes, HDL cholesterol concentrations in the CD36-deficient patients were significantly higher than in the control subjects. The nondiabetic CD36-deficient patients had higher triglyceride concentrations than the control subjects, and triglyceride concentrations were higher in the diabetic CD36-deficient patients than in the nondiabetic CD36-deficient patients. The prevalence of insulin resistance in the nondiabetic CD36-deficient patients was similar to that in the control subjects. CONCLUSIONS: Human CD36 deficiency is not necessarily responsible for insulin resistance. Lipid abnormalities in CD36 deficiency may partly depend on the presence of diabetes, and increased levels of triglyceride and HDL cholesterol may be due to impaired binding of fatty acids and HDL to CD36 and subsequent clearance.

Aged↗

PubMed2002

Effects of neutral endopeptidase 24.11 inhibition on myocardial infarct size and ischemic preconditioning in rabbits.

This study was designed to determine whether inhibition of neutral endopeptidase 24.11 (NEP) reduces infarct size and enhances protection afforded by ischemic preconditioning (PC) by elevation of the tissue bradykinin (BK) level in the heart in situ. In experiments to determine a dose of thiorphan (Thio) that inhibits NEP activity in the rabbit, infusion of Thio at a rate of 15 micro g/kg per min was found to be NEP-selective, since it increased the extent and duration of hypotension after BK injection (50 ng/kg and 100 ng/kg, i.v.) but did not inhibit pressor response to angiotensin I (100 ng/kg and 500 ng/kg, i.v.). Infusion of Thio at a rate of 25 micro g/kg per min blunted pressor response to angiotensin I by 30%, suggesting this dose partially inhibits angiotensin-converting enzyme activity. In the second series of experiments, myocardial infarction was induced by 30-min coronary occlusion and 3-h reperfusion in rabbits. In untreated controls, infarct size as a percentage of area at risk (%IS/AR) was 50.1+/-4.1%, and infusion of Thio at 15 micro g/kg per min and 25 micro g/kg per min failed to limit infarct size (54.3+/-4.0% and 50.1+/-2.8%, respectively). However, these doses of Thio significantly reduced %IS/AR when combined with PC with 2-min ischemia to 25.7+/-3.3% and 19.7+/-3.1%, respectively, although this submaximal PC protocol alone did not achieve significant cardioprotection (%IS/AR=35.6+/-4.0%). This effect of Thio on PC was abolished by pretreatment with icatibant (2 micro g/kg), a BK B(2) receptor blocker. The results of the present study suggest that NEP inhibition does not increase anti-infarct tolerance of the myocardium but significantly enhances cardioprotection of PC via a B(2) receptor-mediated mechanism.

Animals↗

PubMed2002

Glycosaminoglycans affect the action of human plasma kallikrein on kininogen hydrolysis and inflammation.

Human plasma kallikrein (huPK) is a serine proteinase involved in many biological processes including those of the kallikrein-kinin system. The action of huPK on kininogen results in bradykinin (BK) release, a potent mediator of inflammatory responses. BK generation may be influenced by several agents, and the aim of this work was to investigate the effect of glycosaminoglycans (GAGs) on human high-molecular-weight kininogen (HK) hydrolysis by huPK and on inflammation. huPK was pre-incubated in the absence and presence of different GAGs, followed by the addition of kininogen. Bradykinin released at different times was measured by radioimmunoassay, and KM and kcat were calculated. Tuna and bovine dermatan sulfates, the most potent GAGs studied, reduced by 80% and 68%, respectively, the catalytic efficiency of huPK (control = 4. x 10(4) M(-1) s(-1) in BK release. The effect of bovine dermatan sulfate (BDS) on inflammatory response was studied in rat paw edema induced by carrageenin and hourly determined (1-4 h) by plethysmography. BDS significantly reduced the inflammatory response in the first and second hours of measurements (24% and 28%, respectively), p < 0.05. GAGs were shown to reduce bradykinin release "in vitro" and in an inflammation model. This reduction may play a role in the control or maintenance of some pathological and physiological processes.

Animals↗

PubMed2002

Sonoclot coagulation analysis: new bedside monitoring for determination of the appropriate heparin dose during haemodialysis.

BACKGROUND: Thrombotic and haemorrhagic complications affect cardiovascular morbidity and mortality in haemodialysis patients. We investigated whether a new bedside Sonoclot analysis is useful for determining an appropriate heparin dose during haemodialysis. METHODS: Twenty-two haemodialysis patients (15 males and seven females) treated with unfractionated heparin were recruited. Sonoclot parameters, including activated clotting time (ACT), clot rate (CR), time to peak (TP) and peak amplitude (PA), were examined before and after haemodialysis, coupled with conventional coagulable variables, platelet count and fibrinogen level. Some indices were determined and verified to control heparin dose. Thrombotic and haemorrhagic complications were observed for 3 months. Sonoclot analysis was subsequently performed before initiation, 1 h later, 2.5 or 3 h later (before cessation of heparin infusion), and at the end of haemodialysis. RESULTS: Both CR and PA were positively correlated with platelet count and fibrinogen level. Sonoclot parameters except for PA were significantly correlated with heparin dose. Heparin dose was reduced without causing complications in 12 patients with DeltaACT >/=40 s and/or CR after haemodialysis (CRpost) <20 U/min. Thrombotic complications occurred in five patients who had CRpost >30 U/min. ACT and TP increased during heparin treatment. ACT was reversed but TP did not change after cessation of heparin. CR significantly decreased after initiation of heparin and was reversed, although not completely, after cessation of heparin. PA showed no significant changes during haemodialysis. CONCLUSIONS: Sonoclot analysis can monitor accurate coagulable states and determine an appropriate heparin dose during haemodialysis.

Blood Coagulation Tests↗

PubMed2002

Effect of TNF-alpha--converting enzyme inhibitor on insulin resistance in fructose-fed rats.

Insulin resistance is associated with hypertension, obesity, dyslipidemia, and type 2 diabetes. It is well known that tumor necrosis factor (TNF)-alpha is one of the factors linked to obesity-induced insulin resistance; however, there have been no reports on the role of TNF-alpha in insulin resistance in nonobese insulin-resistant hypertensives. We tested the hypothesis that TNF-alpha affects insulin resistance in nonobese insulin-resistant hypertensive fructose-fed rats (FFR) and that a TNF-alpha--converting enzyme (TACE) inhibitor that blocks TNF-alpha secretion improves insulin resistance in FFR. Six-week-old male Sprague-Dawley rats were fed either standard chow (control) or fructose-rich chow (FFR) for 6 weeks. For the last two weeks of a six-week period of either diet, the rats were treated with a vehicle (control or FFR) or a TACE inhibitor (100 mg/kg/d of KB-R7785; FFR+TACE-I) in peritoneal injection. At the age of 12 weeks, insulin sensitivity was assessed in all conscious rats by the euglycemic hyperinsulinemic glucose clamp technique. While FFR had higher blood pressure than the control rats (P<0.01), the TACE inhibitor did not change blood pressure. Insulin sensitivity (M-value) was reduced in FFR compared with that in the control rats (16.7 +/- 1.1 mg/kg per min and 10.3 +/- 0.6 mg/kg per min in the control rats and FFR, respectively, P<0.001), and the TACE inhibitor improved insulin sensitivity to the level of the control rats (14.3 +/- 1.2 mg/kg per min in FFR+TACE-I, P<0.01). These data indicate that TNF-alpha plays a major role in insulin resistance in nonobese insulin-resistant models and also suggest that TACE would be a good target for controlling insulin resistance not only in obese models but also in nonobese insulin-resistant models.

ADAM Proteins↗