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Biomedical subjects

S Nambu

Publications and source records attributed to S Nambu.

At least 55 records · Page 3Linked to original sources

3,5,3'-Triiodothyronine regulates insulin level in the circulation following glucose ingestion in humans.

To clarify the relationship between the 3,5,3'-triiodothyronine (T3) response and the insulin response after glucose ingestion in humans, serum T3, immunoreactive insulin (IRI), C-peptide immunoreactivity (CPR), nonesterified fatty acid (NEFA) and plasma glucose levels were measured in 11 nonobese inpatients with normal glucose tolerance after oral 75 g glucose tolerance test. Ingestion of the glucose solution significantly increased serum T3 levels from 120.1 +/- 4.1 ng/dl to 132.5 +/- 4.4 ng/dl (P less than 0.01) at 60 min after glucose ingestion and it continued to increase after 3 h. Serum IRI and CPR levels peaked at 60 min (P less than 0.01, respectively) after glucose ingestion and they also continued to increase after 3 h. Plasma glucose levels peaked at 30 min (P less than 0.01) after glucose ingestion and then decreased to basal level after 3 h. Negative correlation was found between sigma T3 level and sigma IRI level (r = -0.75), and between sigma T3 level and sigma IRI/sigma glucose ratio (r = -0.88). Negative correlation was also found between basal T3 level and sigma IRI level (r = -0.82). No correlation was found between sigma T3 level and sigma CPR level. Positive correlation was found between sigma glucose level and sigma dT3 level (r = 0.74), and between sigma dglucose level and sigma dT3 level (r = 0.81). The findings suggest that T3 regulates insulin level in the circulation after glucose ingestion and the increase in serum T3 levels after glucose ingestion is necessary for the glucose removal from the circulation in humans.

Adult↗

Effect of atenolol on serum beta 2-microglobulin level in hypertensive diabetic patients.

The effects of atenolol (50 mg once daily) on serum beta 2-microglobulin levels in 11 hypertensive diabetic patients uncomplicated by renal dysfunction were studied. Atenolol significantly decreased serum beta 2-microglobulin levels (micrograms/mL) at four weeks (1.5 +/- 0.13) and at eight weeks (1.4 +/- 0.09) from pretreatment level (1.8 +/- 0.17) (P less than 0.05, respectively), along with statistically significant antihypertensive effects. Blood urea nitrogen, serum creatinine, fasting plasma glucose, HbA1C levels, and body weight remained unchanged. The results suggest that atenolol provides a favorable effect on renal function in hypertensive diabetic patients uncomplicated by renal dysfunction.

Atenolol↗

Tumorigenicity study of disodium glycyrrhizinate administered orally to mice.

Disodium glycyrrhizinate (DG) was administered at concentrations of 0.15 (maximum tolerated dose), 0.08, 0.04 or 0% in the drinking-water to groups of 50, 70, 60 and 60 male B6C3F1 mice, respectively. Female groups, each consisting of 50 mice, were given DG in the drinking-water at concentrations of 0.3 (maximum tolerated dose), 0.15, 0.08 or 0%. Treatment was continued for 96 wk and the experiment was terminated at wk 110. There was no difference between treated and control groups in tumour incidence, in the latent period before tumours appeared or in the distribution of different types of tumour. Thus the long-term oral administration of DG to mice did not yield any evidence of chronic toxicity or tumorigenicity.

Administration, Oral↗

Hormonal regulation of glandular kallikrein activity and its inhibitor in human plasma.

Plasma glandular kallikrein (GK) activity, serum 3,5,3'-triiodothyronine (T3), thyroxine (T4), reverse T3, thyroid-stimulating hormone, plasma alpha 2 macroglobulin (alpha 2M) and alpha 1 antitrypsin (alpha 1AT) levels were determined in 29 non-diabetic female subjects given normal ad-lib diet or one of several kinds of caloric composition for more than 7 days after an overnight fast. Positive exponential correlation was found between serum T3 level and plasma GK activity (r = 0.54), and there was positive linear correlation between serum T3 level and plasma alpha 2M level (r = 0.51). Positive natural logarithmic correlation was found between plasma GK activity and plasma alpha 2M level (r = 0.47). There was no correlation between plasma GK activity and plasma alpha 1AT level, and between serum T3 level and plasma alpha 1AT level. No correlation was found between serum T4 level and plasma GK activity, and between serum T4 level and plasma alpha 2M level. There was no correlation between serum T4 and T3 level, but positive exponential correlation was found between serum T4 and reverse T3 level (r = 0.82). These data suggest that T3 responds to dietary carbohydrate through Kallikrein-Kinin system, and T3 regulates both GK activity and its inhibitor (alpha 2M) in human plasma.

Adult↗

A new isoform of apolipoprotein E--apo E-5--associated with hyperlipidemia and atherosclerosis.

Heterogeneity of apolipoprotein E (apo E) was analyzed by isoelectric focusing of apo VLDL in patients with hyperlipidemia and/or atherosclerosis. Six major apo E phenotypes were shown, in agreement with the current genetic model which is composed of 3 major apo E isoproteins, apo E-4, apo E-3 and apo E-2, resulting from three apo E alleles, epsilon 4, epsilon 3 and epsilon 2, at a single genetic locus. We recognized an additional apolipoprotein band, which is located basic to apo E-4 on an isoelectric focusing gel, in 3 patients with hyperlipidemia. The new apolipoprotein component, named apo E-5, was identical with ordinary apo E in apparent molecular weight by SDS-polyacrylamide gel electrophoresis and in its interactions with heparin-Sepharose gel and with anti-apo E antibody. This mutant apo E isoprotein had an isoelectric point more basic by one unit of charge than apo E-4. Two of 3 patients had the phenotype E5/3, and the other the phenotype E5/4. Genetic analysis of the apo E phenotypes in family members of the patients indicated the presence of a new apo E allele (epsilon 5) at the same genetic locus as hitherto known alleles. Since most of the subjects above 50 years old with apo E-5 had ischemic heart disease or cerebral infarction, it was suggested that the mutant apo E-5 may possibly be related to the development of atherosclerosis.

Apolipoproteins↗

Clofibrate enhances the affinity of insulin receptors in non-insulin dependent diabetes mellitus.

Glucose-lowering mechanism by clofibrate was studied in non-insulin dependent diabetics managed with dietary therapy alone. Clofibrate 1500 mg was administered for 1 month to 15 patients, and 75 g oral glucose tolerance test and insulin tolerance test were carried out before and after 1 month of the treatment. Fasting plasma glucose values were decreased from 9.34 +/- 0.53 mmol/l to 7.58 +/- 0.33 mmol/l (P less than 0.01), and fasting insulin levels were decreased from 13.8 +/- 1.7 microunits/ml to 10.1 +/- 1.5 microunits/ml (P less than 0.05). However, insulinogenic index and sigma IRI/sigma glucose ratio during 75 g oral glucose tolerance test were not changed. Enhanced glucose fall in insulin tolerance test was also observed. As these results suggested the enhanced tissue sensitivity to insulin, we examined the insulin binding to erythrocytes before and at 3 months' treatment of clofibrate in 10 non-insulin dependent diabetics. Insulin bindings were increased from 3.41 +/- 0.17% to 4.11 +/- 0.20% in the presence of 1 ng/ml of native insulin (P less than 0.01). This increased binding was due to an increased affinity without a change in the number of insulin receptors. These results suggest that improved glucose tolerance by clofibrate might be derived from the enhanced tissue sensitivity to insulin, probably through an enhanced affinity of insulin receptors.

Blood Glucose↗

New mutants of apolipoprotein E associated with atherosclerotic diseases but not to type III hyperlipoproteinemia.

We analyzed the heterogeneity of apo E in very low density lipoprotein from 58 hyperlipidemic subjects with or without atherosclerosis, 69 patients with ischemic heart disease, and 100 apparently healthy individuals. Apo E gene frequencies in the group of healthy individuals were comparable with those in German and American populations. The distribution of six common apo E phenotypes in the groups of hyperlipidemia and ischemic heart disease was similar to that in the healthy group. In addition to the three major isoforms of apolipoprotein E (apo E-4, E-3, and E-2) and the new one (apo E-5) which was recently found in this laboratory, we have discovered an additional series of components, which showed themselves as at least three bands on an isoelectric focusing gel in the region of E-VII through E-V, in four patients with hyperlipidemia and atherosclerosis. The new series of apo E components, named apo E-Suita, was identical with the ordinary apo E in its interaction with heparin-Sepharose gel and with anti-apo E antibody. The most basic component of apo E-Suita (E-VII) was the unsialylated form and other components (E-VI and E-V), the sialylated forms. Family studies revealed that apo E-Suita was determined by inheritance of a new apo E allele located at the same locus as the hitherto known apo E components. Apo E-5 and apo E-Suita isoproteins had isoelectric points more basic than apo E-3, the parent type, by two and four units of charge, respectively. While the apo E-Suita isoprotein had the same molecular weight as ordinary major apo E isoproteins, the molecular weight of the apo E-5 isoprotein was approximately 1,500-2,000 lower than the other apo E isoproteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The incidence of abnormal apo E components, including apo E-5 and apo E-Suita, was high among patients with hyperlipidemia and ischemic heart disease (7:127), while we could not find such components among 100 healthy individuals. Moreover, five of seven patients with the abnormal apo E had overt atherosclerotic disease. The findings suggest that these kinds of apolipoprotein mutation are closely related to the development of atherosclerosis.

Antigen-Antibody Reactions↗

The effects of insulin on the cardiovascular system in patients with coronary heart disease.

In order to clarify the effects of insulin on the cardiovascular system in patients with and without coronary heart disease (CHD), we studied the changes of electrocardiogram (ECG), blood pressure, pulse rate, along with those of blood glucose, free fatty acid, immunoreactive insulin, cortisol and potassium during insulin tolerance test (ITT). The presence or absence of CHD was verified by the coronary angiography and various stress testings beforehand. In patients with CHD, ischemic ST-T wave changes were recorded following the increment of double product after insulin injection and these changes were quite similar to those recorded during exercise test. In patients without CHD, although hypoglycemia and suppression of lipolysis were achieved, ischemic ST-T wave changes were not recorded after insulin injection. Furthermore, in a patient with Triple Vessel Disease, ischemic changes of ECG provoked by ITT were abolished completely by the administration of nifedipine and propranolol. ITT may induce ischemic changes of ECG in patients with CHD by different mechanisms from those of exercise tests and it may provide a useful tool for the diagnosis of CHD in clinical applications.

Aged↗

Supravalvular aortic stenosis and coronary ostial stenosis in familial hypercholesterolemia: two-dimensional echocardiographic assessment.

The lesions of the aortic root, which are supravalvular aortic stenosis and coronary ostial stenosis, in familial hypercholesterolemia were studied using two-dimensional echocardiography. The subjects were 25 heterozygotes, six homozygotes and 30 control subjects. The internal diameters of the aortic ring, the sinus of Valsalva and the supravalvular aortic ring were measured. Measurement variation due to body size was avoided by normalizing the latter two values by the diameter of the aortic ring. Four heterozygotes and all homozygotes were judged to have stenosis of the supravalvular aortic ring; none of heterozygotes and four homozygotes had stenosis of the sinus of Valsalva. In three of the four patients with stenosis of both the supravalvular aortic ring and the sinus of Valsalva, a pressure gradient was demonstrated. The degree of supravalvular aortic stenosis correlated with the serum cholesterol level but not with patient age. All homozygotes, even very young ones, had a severe aortic root lesion. In the short-axis view of the aortic root, a lump (raised mass) on the aortic wall indicating atheromatous plaquing was demonstrated in five heterozygotes and all homozygotes. Coronary ostial stenosis was shown in three of the four patients whose plaquing echoes were adjacent to the coronary orifice. We conclude that two-dimensional echocardiography is useful in diagnosing lesions of the aortic root in patients with hypercholesterolemia.

Adolescent↗

Coronary artery disease in heterozygous familial hypercholesterolemia.

Serum lipids, lipoproteins and Achilles tendon thickness in 52 patients with heterozygous familial hypercholesterolemia (FH) were investigated in order to clarify what are the important factors for the development of coronary artery disease (CAD) in heterozygous FH patients. There were no significant differences in the average concentration of total cholesterol and triglyceride between the patients with and those without CAD. The HDL cholesterol (HDL-C) level was significantly lower in patients with CAD than in those without, and the HDL-C value was within the normal range in most of the patients with heterozygous FH, if not associated with CAD. Although most of the males aged over 50 years had CAD and a decreased level of HDL-C, many of the aged females were without signs of CAD. The HDL-C value of heterozygous FH patients with CAD was significantly lower compared with the age-matched group without CAD. The Achilles tendon was thicker in patients with CAD than in those without CAD, both for males and females, although it was less closely correlated with the incidence of CAD than HDL-C or the atherogenic index. A forecast concerning the development of CAD in heterozygous FH may be possible if we consider multiple parameters, such as HDL-C, atherogenic index, Achilles tendon thickness, etc.

Achilles Tendon↗

Coma preceded by severe dysphagia in type II diabetes mellitus.

A 62-year-old man with 11 years' duration of type II diabetes was hospitalized because of non-ketotic diabetic coma. He had never noted any symptoms of swallowing difficulty until 3 days before admission when they developed gradually and he became comatous. He had never received special medication such as diuretics except anticonvulsants. Even after the recovery from diabetic coma he could hardly swallow solid foods or saliva for about 15 days, but these symptoms subsided gradually. Motility dysfunction of esophagus and pharynx in diabetes mellitus, in most cases they are mild, has been described, although diabetic coma preceded by dysphagia has not been documented except in one report. We studied, therefore, the autonomic nerve function of the present patient and discussed the relationship between dysphagia and diabetic coma together with the description of the clinical course of this patient. The relationship between this case and the previously reported cases were compared in terms of the sex, age, type of diabetes, clinical course, medication and the autonomic nerve function.

Autonomic Nervous System Diseases↗

Changes of glandular kallikrein activity in human plasma following glucose ingestion.

We studied the changes of glandular kallikrein activity in plasma of nine normal female volunteers, aged 22.2 +/- 1.20 years (mean +/- SEM), following 75 g glucose ingestion along with those of immunoreactive insulin, C-peptide immunoreactivity, free fatty acid and blood glucose using our recently developed assay system for plasma glandular kallikrein activity. Glandular kallikrein activities decreased initially from mean baseline level and then returned to baseline level with the lapse of time after glucose load. Furthermore, in hyperinsulinemic group, mean glandular kallikrein activities at 120 min after glucose load revealed to be significantly higher than those of normoinsulinemic group. The findings suggest that active glandular kallikrein is consumed and utilized during glucose uptake at the peripheral tissues, and hyperinsulinemia brings about prolonged activation of kallikrein-kinin system.

Adult↗