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Biomedical subjects

Tomoatsu Nakamura

Publications and source records attributed to Tomoatsu Nakamura.

12 recordsLinked to original sources
PubMed2004

Decrease in serum C-reactive protein levels by troglitazone is associated with pretreatment insulin resistance, but independent of its effect on glycemia, in type 2 diabetic subjects.

Insulin-sensitizing thiazolidinediones (TZDs) decrease inflammatory markers such as high-sensitive C-reactive protein (hsCRP) in sera in addition to their hypoglycemic effects. However, factors associated with the decrease in serum hsCRP concentrations are unclear. In the present study, an effect of troglitazone on serum hsCRP levels was investigated and compared with its effect on glycemia. A total of 34 subjects with type 2 diabetes (17 men and 17 women, aged 54+/-2 years and body mass index (BMI) 26.7+/-0.6 kg/m(2), mean+/-S.E.) were studied. Nineteen out of the 34 subjects was treated with troglitazone 400mg daily for 12 weeks. The remaining 15 subjects were treated with metformin 750 mg daily as a control group. Baseline hsCRP levels were comparable between the two groups, and those were positively associated with fasting insulin levels. After treatment, glycemic control assessed by HbA1c and fasting glucose levels improved in both groups, whereas insulin sensitivity index estimated by homeostasis model assessment (HOMA-R) decreased only in the troglitazone-treated group. Serum levels of hsCRP significantly decreased from 916+/-210 ng/ml to 569+/-123 ng/ml (P<0.05) in the troglitazone-treated group, whereas the levels remained unchanged in the metformin-treated group (from 1087+/-248 ng/ml to 1152+/-301 ng/ml). In the troglitazone-treated group, there was no difference in the absolute and percent change in serum hsCRP levels between responders, who displayed the decrease in HbA1c greater than 0.6% (n=12), and the remaining non-responders (n=7). The decrease in serum hsCRP concentrations was negatively related to baseline levels of serum hsCRP and insulin and HOMA-R. In conclusion, troglitazone, but not metformin, reduced serum hsCRP levels in type 2 diabetic patients. The decrease in serum hsCRP concentrations by troglitazone was associated with the pretreatment levels of hsCRP and insulin resistance, but independent of the changes in glycemia.

Blood Glucose↗
PubMed2004

A case of thymic enlargement in hyperthyroidism in a young woman.

We present the case of a 24-year-old woman with thymic enlargement accompanied by hyperthyroidism. An x-ray incidentally detected her thymic enlargement and the size was estimated to be 226 cm(3) by computed tomography (CT) using three-dimensional analysis. Physical examination revealed a soft diffuse goiter, increased sweating and restlessness; thyroid function tests showed hyperthyroidism. Because the possibility of a thymoma could not be completely excluded, a mediastinal biopsy via a supracervical approach was done that determined the specimen was composed of normal thymic tissue. Together with these findings, the patient's thymic enlargement was likely to be consistent with true thymic hyperplasia. Moreover, we have demonstrated the presence of the thyrotropin (TSH) receptor in her thymus using reverse transcription-polymerase chain reaction (RT-PCR). She was treated with methimazole, resulting in the resolution of not only the thyroid dysfunction but also thymic enlargement. Thymic enlargement has often been recognized as a complication of hyperthyroidism. However, the pathophysiologic mechanisms underlying these conditions remain obscure. Our result raises the speculation that the thymus is also a target organ of autoimmune attack as are the orbital and fibroblasts, which lead to Graves' ophthalmopathy and pretibial dermopathy, respectively.

Adult↗
PubMed2004

Effect of moderate exercise training on peripheral glucose effectiveness, insulin sensitivity, and endogenous glucose production in healthy humans estimated by a two-compartment-labeled minimal model.

For examining the effects of moderate exercise training on peripheral glucose effectiveness (S(g)(2)*), insulin sensitivity (S(i)(2)*), and endogenous glucose production (EGP), seven men and one woman (24.8 +/- 1.8 years) participated in cycle ergometer training at lactate threshold intensity for 60 min/day, 5 days/week for 12 weeks. Stable-labeled frequently sampled intravenous glucose tolerance tests were performed before and 16 h and 1 week after the last training session. S(g)(2)* (pre 0.71 +/- 0.03 x 10(-2), 16 h 0.85 +/- 0.02 x 10(-2) dl. kg(-1). min(-1)) and S(i)(2)* (pre 12.6 +/- 2.6 x 10(-4), 16 h 19.7 +/- 3.3 x 10(-4) dl. kg(-1). min(-1). [ micro U/ml](-1)), analyzed using the two-compartment minimal model, were significantly elevated 16 h after the last training session. The elevated S(g)(2)* remained higher despite the cessation of exercise training for 1 week (1.00 +/- 0.03 x 10(-2) dl. kg(-1). min(-1)). EGP was suppressed within 20 min after glucose bolus, and the suppression of EGP was followed by their overshoot. The time course of EGP during the intravenous glucose tolerance test remained similar after the training period. In conclusion, moderate exercise training at lactate threshold improves not only peripheral insulin sensitivity but also peripheral glucose effectiveness with no change in the effect of glucose and/or insulin to suppress EGP in healthy humans.

Adult↗
PubMed2003

Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 diabetes mellitus.

The aim of the present study was to investigate the association of serum adiponectin concentration with regional adiposity and insulin resistance in subjects with type 2 diabetes mellitus. A total of 73 Japanese men with type 2 diabetes (aged 59 +/- 11 years and body mass index [BMI] 23.8 +/- 3.0 kg/m(2), mean +/- SD) were studied. Fasting serum adiponectin and leptin concentrations were determined by radioimmunoassay. Regional adiposity was measured by abdominal computed tomography (CT) at the umbilical level, and insulin resistance was estimated by homeostasis model assessment (HOMA-R). Univariate regression analysis showed that serum adiponectin levels were negatively correlated with subcutaneous and visceral fat areas. With multivariate regression analysis, visceral fat area was a predominant determinant of serum adiponectin levels. In contrast, subcutaneous fat area was strongly associated with serum leptin concentrations. Among subcutaneous and visceral fat areas, BMI, and serum leptin levels, both subcutaneous and visceral fat areas were independently associated with HOMA-R. In another model incorporating serum adiponectin levels, serum adiponectin levels were selected as an independent determinant of HOMA-R instead of visceral fat area. In conclusion, hypoadiponectinemia was associated with visceral fat accumulation rather than subcutaneous fat depot in Japanese men with type 2 diabetes mellitus. Both subcutaneous and visceral fat accumulation contribute to insulin resistance in these subjects, and the contribution of visceral fat may be mediated, in part, by hypoadiponectinemia.

Adiponectin↗
PubMed2003

Relationship between exercise training-induced increase in insulin sensitivity and adiponectinemia in healthy men.

Circulating concentrations of adiponectin, an adipocyte-derived protein, are increased by thiazolidinediones and by weight reduction, accompanied with improvement in insulin sensitivity. The effect of exercise training, another therapy to increase insulin sensitivity (SI), on adiponectinemia is currently unclear. The present study was undertaken to clarify whether exercise training-induced increase in SI is related to changes in adiponectinemia in healthy men. Twelve healthy non-obese men underwent ergometer training at lactate threshold (LT) intensity for 60 min/day for 5 days/week for 6 weeks. An insulin-modified intravenous glucose tolerance test was performed before and at 16 h and 1 week after the last training session to determine SI using a minimal-model approach. Serum levels of adiponectin were determined at the same time. After the exercise training, VO2max and LT were significantly increased by 7.2% and 22.3% (P<0.01), while BMI and body fat mass remained unchanged. SI was significantly increased at 16 h after the last training session (from 7.0 +/- 3.1 to 9.6 +/- 3.6 [x 10(-4) x (microU/ml)(-1) x min(-1)], P<0.01), but returned toward the basal levels at 1 week after the cessation of the training. Serum adiponectin concentrations before the training (20.9 +/- 7.4 microg/ml) were positively correlated with SI. The concentrations were slightly but significantly decreased at 16 h (17.2 +/- 6.6 microg/ml, P<0.05), and returned to the basal values at 1 week after the training. From these results, it can be concluded that exercise training-induced increase in SI is not dependent on the increase in adiponectinemia in healthy men.

Adiponectin↗
PubMed2003

Unilateral adrenalectomy improves insulin resistance and diabetes mellitus in a patient with ACTH-independent macronodular adrenal hyperplasia.

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing's syndrome. Bilateral adrenalectomy is considered to be a standard therapy for AIMAH, although lifetime replacement of glucocorticoids is necessary after the procedure. This paper describes a subject with AIMAH who underwent unilateral adrenalectomy of the predominantly enlarged gland and subsequently displayed an improvement in insulin resistance and diabetes mellitus, the cardinal symptoms before the operation, concomitant with alleviation of abnormal cortisol secretion. The patient was a 61-year-old man with a body mass index of 25.6 kg/m2. He was diagnosed as having diabetes mellitus, hypertension, and hyperlipidemia at 50 years of age. Eight years after diagnosis, bilateral enlargement of the adrenal glands was revealed by chance upon computed tomography of the abdomen. Typical manifestations of Cushing's syndrome were not demonstrated. Basal levels of serum and urinary cortisol had not increased, although the serum cortisol level displayed no circadian rhythm and no response to the administration of dexamethasone. Despite sulfonylurea treatment, the patient's HbA1C level was as high as 7.6% (normal range 4.3-5.8%). Fasting insulin concentration was increased to 42.6 microU/ml, and the homeostasis model insulin resistance index (HOMA-R) was calculated to be 15.5 (with a normal range of less than 2.5), indicating severe insulin resistance. Unilateral adrenalectomy of the predominantly enlarged gland revealed that the resected gland consisted of multiple nodules of various sizes. Based on endocrinological, radiological, and pathological findings, a diagnosis of AIMAH was made. Ten months after the unilateral adrenalectomy, cortisol circadian rhythms were restored, and serum cortisol concentration was suppressed in response to the administration of low doses of dexamethasone, suggesting an improvement in the cortisol secretory pattern. Levels of HbA1C, fasting insulin, and HOMA-R decreased to 5.7%, 12.7 microU/ml, and 2.2, respectively. An improvement in hyperlipidemia was also observed. Insulin resistance and glucose intolerance are recognized as features of mild hypercortisolism. In the present case, unilateral adrenalectomy was effective in ameliorating insulin resistance and improving glycemic control. Unilateral adrenalectomy might be an alternative therapy for improvement of glucose and lipid metabolism in subjects with AIMAH.

Adrenal Gland Diseases↗
PubMed2003

Close association of severe hyponatremia with exaggerated release of arginine vasopressin in elderly subjects with secondary adrenal insufficiency.

OBJECTIVE: Hyponatremia occurs not infrequently in hypopituitarism. Arginine vasopressin (AVP)-induced impaired water excretion is found in patients with hypopituitarism and experimental models of glucocorticoid deficiency. DESIGN: The present study was undertaken to determine whether augmented release of AVP is involved in the development of hyponatremia in elderly subjects with secondary adrenal insufficiency. METHODS: Forty patients with ACTH-deficient, secondary adrenal insufficiency were examined. They were divided into three groups according to the age at which diagnosis was ascertained (group A <20 Years, group B 20-64 Years, and group C>or=65 Years). RESULTS: Hyponatremia was more manifest in the elderly group than in the other two groups, serum sodium (Na) levels being 124.7 mmol/l in the elderly group, a value significantly less than 141.5 and 133.5 mmol/l in groups A and B. Plasma AVP levels seemed likely to be high compared with the respective hypo-osmolality in plasma in the elderly group, as plasma AVP levels were 1.7 pmol/l despite a mean plasma osmolality of 259 mmol/kg. Such an alteration was less clear in group B and was not found in group A. Therefore, elevation of plasma AVP was apparent in the elderly patients. Hydrocortisone replacement promptly normalized serum Na levels from 125 to 142 mmol/l (P<0.01) and reduced plasma AVP levels from 1.7 to 0.9 pmol/l (P<0.05), which were comparable to the respective plasma osmolality in the elderly patients. CONCLUSION: These results indicate that non-suppressible release of AVP is crucially involved in the impaired water excretion and hyponatremia seen in elderly patients with secondary adrenal insufficiency compared with the younger patients, and that exaggerated release of AVP becomes manifest as the subjects grow older.

Adolescent↗
PubMed2002

S(G), S(I), and EGP of exercise-trained middle-aged men estimated by a two-compartment labeled minimal model.

To examine the effects of physical training on glucose effectiveness (S(G)), insulin sensitivity (S(I)), and endogenous glucose production (EGP) in middle-aged men, stable-labeled frequently sampled intravenous glucose tolerance tests (FSIGTT) were performed on 11 exercise-trained middle-aged men and 12 age-matched sedentary men. The time course of EGP during the FSIGTT was estimated by nonparametric stochastic deconvolution. Glucose uptake-specific indexes of glucose effectiveness (S(2*)(G) x 10(2): 0.81 +/- 0.08 vs. 0.60 +/- 0.05 dl. min(-1). kg(-1), P < 0.05) and insulin sensitivity [S(2*)(I) x 10(4): 24.59 +/- 2.98 vs. 11.89 +/- 2.36 dl. min(-1). (microU/ml)(-1). kg(-1), P < 0.01], which were analyzed using the two-compartment minimal model, were significantly greater in the trained group than in the sedentary group. Plasma clearance rate (PCR) of glucose was consistently greater in the trained men than in sedentary men throughout FSIGTT. Compared with sedentary controls, EGP of trained middle-aged men was higher before glucose load. The EGP of the two groups was similarly suppressed by approximately 70% within 10 min, followed by an additional suppression after insulin infusion. EGP returned to basal level at approximately 60 min in the trained men and at 100 min in the controls, followed by its overshoot, which was significantly greater in the trained men than in the controls. In addition, basal EGP was positively correlated with S(2*)(G) . The higher basal EGP and greater EGP overshoot in trained middle-aged men appear to compensate for the increased insulin-independent (S(2*)(G)) and -dependent (S(2*)(I)) glucose uptake to maintain glucose homeostasis.

Adult↗
PubMed2002

Urinary excretion of aquaporin-2 water channel in diabetic ketoacidosis.

We studied the changes in plasma arginine vasopressin (AVP) and urinary excretion of aquaporin-2 (UAQP-2) water channel in 3 patients with diabetic ketoacidosis. They had marked hyperglycemia of 27.9 +/- 2.8 mmol/l (mean +/- SEM), and elevated hemoglobin A1c of 8.8 +/- 1.4%. Circulatory blood volume was decreased by approximately 25%, which was determined by the changes in hematocrit. Plasma AVP levels were elevated to 10.3 +/- 3.0 pmol/l and UAQP-2, 578 +/- 200 fmol/mg creatinine (normal, 153 +/- 28) at the hospitalization. When hyperglycemia was improved by the intravenous infusion of a small dose of insulin plus fluid administration, both plasma AVP and UAQP-2 promptly decreased to 1.2 +/- 0.2 pmol/l and 252 +/- 29 fmol/mg creatinine on day 7, respectively. These alterations were concomitant with the recovery of circulatory blood volume. In the present study, UAQP-2, in addition to plasma AVP, indicates circulatory blood volume depletion, and the changes in UAQP-2 estimates the AVP-dependent recovery of circulatory blood volume during the therapeutic period in the patients with diabetic ketoacidosis.

Adult↗
PubMed2002

Decrease in urinary excretion of aquaporin-2 associated with impaired urinary concentrating ability in diabetic nephropathy.

Aquaporin-2 (AQP-2) is known to be expressed in the renal collecting duct cells and participates in urinary concentration in response to arginine vasopressin (AVP). The present study was undertaken to determine whether progression of renal dysfunction affects urinary excretion of AQP-2 in diabetic nephropathy. The study was composed of 8 control subjects and 14 patients with type 2 diabetes classified into two groups according to serum creatinine level (cut-off point; 1.5 mg/dl). After an 8-hour water deprivation, both urinary osmolality (U(osm)) and urinary excretion of AQP-2 significantly decreased in the diabetic patients with chronic renal failure as compared to the control subjects (p < 0.0001, p < 0.05, respectively). After a water load (10 ml/kg), no differences were found in plasma osmolality (P(osm)), AVP levels and U(osm), whereas urinary excretion of AQP-2 significantly decreased in the patients with chronic renal failure as compared to the control subjects (p < 0.05). These results indicate that the decreased urinary excretion of AQP-2 in diabetic nephropathy is due to the impaired cellular signaling of AVP in collecting duct cells, which may be partly involved in the urinary concentrating defect in renal failure.

Aquaporin 2↗