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Biomedical subjects

Shigeru Nakano

Publications and source records attributed to Shigeru Nakano.

7 recordsLinked to original sources
PubMed2003

Insulin resistant state in type 2 diabetes is related to advanced autonomic neuropathy.

To elucidate the relationships between obesity, glycemic control, dyslipidemia, hypertension, microvascular complications, and insulin resistance assessed using an euglycemic hyperinsulinemic clamp technique, we studied 54 hospitalized type 2 diabetic subjects (DM) and 10 age- and sex-matched normotensive, nonobese control subjects (C). Glucose infusion rate (GIR) derived from the clamp study was used as an index of insulin resistance. Body mass index (BMI), the prevalence of hypertension, HbA1c and serum nonesterified fatty acids (NEFA) were significantly higher, and serum high-density-lipoprotein (HDL)-cholesterol was significantly lower in DM than in C (p < 0.05 or less). The median GIR level was significantly lower inDM than in C (p = 0.038). The difference in GIR between the two groups wasstill statistically significant even after adjustment for BMI, mean BP, HbA1c, NEFA, and HDL-cholesterol. However, after simultaneous adjustment for these factors, there was no difference in GIR between the two groups. Body mass index, mean BP, HbA1c, and NEFA showed negative correlations, and serum HDL-cholesterol showed a positive correlation with GIR, but neither age nor duration of diabetes correlated with GIR. When GIR values in DM were divided according to the degree of neuropathy, retinopathy, and nephropathy, and compared to those in C, GIR levels tended to be decreased with increasing severity of each microvascular complication, but there was no difference in median GIR levels among the diabetic subgroups. Relationships between the GIR levels and confounding factors such as age, sex, BMI, mean BP, HbA1c, serum NEFA, and serum HDL-cholesterol, were examined simultaneously with a multiple regression analysis. This analysis revealed that HbA1c and serum NEFA may affect the GIR level. Furthermore, together with these two factors, the relationships between the GIR levels and the severity of each microvascular complication were explored with the same analysis. This model clearly demonstrated that both the decreased CVR-R and pronounced orthostatic fall in systolic BP were independent factors for the decreased GIR. These findings suggest that marked autonomic dysfunction, rather than other confounding factors, is related to increased insulin resistance in DM.

Adult↗
PubMed2003

A practical procedure for achieving a steady state of NOx concentration in plasma: with special reference to the NOx content of Japanese daily food.

To establish a concrete procedure to achieve a steady state plasma NOx concentration with Japanese daily food, NOx contents of about 200 types of food and beverages consumed daily were measured and NOx concentration in plasma was monitored till steady state after various degree of intake of NOx restricted food. The NOx content was found to be high in dark green leaved vegetables and low in grains, processed food, fresh and processed seafood. Tap water and mineral water were found to contain various amounts of NOx that were drastically reduced by treatment with a reverse osmosis column and remained in trace amounts after ion exchange column treatment. NOx content was low in drinks such as cola, but was extremely high in vegetable juice containing dark green leaved vegetables. The intake of high NOx drinks resulted in elevated plasma NOx concentration, but intake of low NOx drinks did not change the plasma NOx concentration. Based on these findings, a steady state could be achieved by 18 hours fasting after the intake of a moderately NOx-restricted diet (about 370, micromoles/day) and by 13 hours fasting after the intake of an extremely NOx-restricted diet (< 100 micromoles/day). NOx concentrations in randomly collected blood samples without these conditions were sometimes ten times higher than that at steady state. This procedure can be undertaken under normal Japanese daily life and is expected to be applicable even to outpatients.

Adult↗
PubMed2002

Testosterone inhibits tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression in human aortic endothelial cells.

We investigated the effect of testosterone (T) on tumor necrosis factor-alpha (TNF-alpha)-induced expression of vascular cell adhesion molecule-1 (VCAM-1) in human aortic endothelial cells. Incubation of these cells with T resulted in a dose-dependent reduction in the expression, with this reduction completely abolished by a selective androgen receptor blocker. Electrophoretic mobility shift assay demonstrated that T inhibited TNF-alpha-induced activation of the transcriptional nuclear factor-kappaB, which is critical for the inducible expression of VCAM-1, probably through the suppression of the nuclear translocation. Our results may suggest an inhibitory effect of T on atherogenesis, providing a novel insight into the consideration of the pathogenesis of atherosclerosis.

Aorta↗
PubMed2002

Paradoxical decrease in plasma NOx by L-arginine load in diabetic and non-diabetic subjects.

L-arginine, a substrate of nitric oxide synthase, was infused (30 g/300 ml/30 min) to patients with or without type 2 diabetes to examine whether or not endothelial dysfunction expressed as attenuated depressor response to the substrate in diabetic patients may accompany attenuated plasma NOx (NO2- and NO3-; an index of NO formation) elevation. Decrease in blood pressure by L-arginine was significantly smaller in diabetic patients than that in non-diabetic patients, and increase in plasma cGMP level in diabetic patients tended to be smaller and retarded than non-diabetic patients. However, plasma NOx decreased in both groups in a similar degree without changes in urinary NOx excretion, implying that NOx in plasma moved to other compartments. These results indicate that plasma NOx could not be solely used as an index of NO formation by L-arginine load and that this paradoxical decrease in plasma NOx would require further examination extending to other NOx compartments.

Arginine↗
PubMed2002

Thrombospondin expression in aldosterone-producing adenomas.

Thrombospondin (TSP) 1 and 2 are extracellular matrix proteins that appear to play a role in cell adhesion and cell migration. It has been demonstrated that the pattern of TSP expression is shifted from TSP1 to TSP2 under adrenocorticotrophic hormone treatment in bovine adrenocortical cells. We investigated the expression in human adrenal tissues by Northern blot analysis and correlated these data with the expression of the adrenocorticotrophic hormone-receptor (ACTH-R). All adrenal tissues (control adrenals, nonfunctional adenomas and ACTH-dependent aldosterone-producing adenomas (APA)) expressed both TSP1 and TSP2 mRNAs. Compared to control adrenals (TSP1 and TSP2 expression = 100 +/- 12%, respectively), TSP1 expression was negatively (51 +/- 10%, p < 0.01) and TSP2 expression was positively (289 +/- 36%, p < 0.01) regulated in APA. No significant differences in TSP1 and TSP2 expressions were found between control adrenals and nonfunctional adenomas. In APA, TSP1 (r = -0.86, p<0.01) and TSP2 (r = 0.88, p < 0.01) expressions correlated closely with the expression of ACTH-R. These results suggest that ACTH activity plays an important role in regulating the expression of TSPs in human adrenal tissues. We speculate that the shift of expression observed in APA may be associated with the phenotype of the tumors.

Adenoma↗
PubMedDate not supplied

Insulin resistance is associated with reduced nocturnal falls of blood pressure in normotensive, nonobese type 2 diabetic subjects.

To assess the relationship between insulin resistance and ambulatory blood pressure (BP) pattern, we determined glucose infusion rate (GIR) as a marker of insulin resistance using a glucose clamp method, and measured 24-h BPs in 25 normotensive, nonobese type 2 diabetic subjects. They were divided into two groups: 11 dippers and 14 nondippers. Clinical characteristics were similar in the two groups except for orthostatic fall in systolic BP. The median GIR level was significantly lower in nondippers than in dippers (P < 0.05). Spearman's rank correlation revealed that the GIRs were negatively correlated with the systolic, diastolic and mean BPs during nighttime (P < 0.05 or less), but not with daytime or whole day BPs. Moreover, based on a logistic regression analysis, the GIR as well as orthostatic fall in systolic BP discriminated independently between dippers and nondippers. Thus, our results suggest that insulin resistance is associated with decreased nocturnal BP fall in type 2 diabetic subjects.

Adolescent↗