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N Sakane

Publications and source records attributed to N Sakane.

At least 37 records · Page 2Linked to original sources
PubMed1997

Beta 3-adrenergic-receptor polymorphism: a genetic marker for visceral fat obesity and the insulin resistance syndrome.

We investigated whether the polymorphism of the beta 3-adrenergic receptor (beta 3-AR) gene, which is associated with insulin resistance in non-diabetic subjects and an earlier onset of non-insulin-dependent diabetes mellitus in Pima Indians, was associated with visceral fat obesity and features of the insulin resistance syndrome in Japanese premenopausal obese women. There was no difference between 131 obese women and 256 control subjects (0.23 vs 0.17, p = 0.112) in the frequency of the Arg64 allele. The visceral fat area measured by computerised tomography scan was greater in homozygous Arg64Arg (172 +/- 17 cm2, n = 6) and heterozygous Trp64Arg (178 +/- 47 cm2, n = 48) women than in women homozygous for the Trp64Trp (121 +/- 46 cm2, n = 77) genotype (p < 0.01). This was also reflected by increased total body fat but not by increased body mass index. The association between the Trp64 allele and visceral fat mass by multiple regression analysis, was independent of age, body mass index and total fat mass (p < 0.004). Moreover, homozygous carriers of the Arg64 allele had higher systolic blood pressure, higher fasting and post-load glucose and insulin concentrations, higher cholesterol, and triglyceride and lower HDL-cholesterol concentrations than homozygous carriers of the Trp64 allele. Some of these differences were also observed between heterozygous Trp64Arg and homozygous Trp64Trp genotypes (glucose tolerance, insulin and cholesterol concentration). We conclude that in obese women the beta 3-AR polymorphism may be used as a genetic marker for visceral fat obesity and the insulin resistance syndrome.

Adipose Tissue↗
PubMed1997

Effect of CL316,243, a highly specific beta(3)-adrenoceptor agonist, on lipolysis of epididymal, mesenteric and subcutaneous adipocytes in rats.

To clarify whether a beta(3)-adrenoceptor agonist is more lipolytic in the visceral adipocytes than in the subcutaneous adipocytes, the lipolysis induced by CL316,243, a highly specific beta(3)-adrenoceptor agonist (relative selectivities of 0, 1 and 10,000 for beta(1)-, beta(2)- and beta(3)-receptors, respectively) was investigated in adipose tissue from rats. White adipocytes were prepared from the subcutaneous, mesenteric, and epididymal white adipose tissues of male Wistar rats (weighing about 150 g). Our findings showed that lipolysis of white adipocytes was stimulated both by the non-specific beta-adrenoceptor agonist, isoproterenol, and by the beta(3)-specific adrenoceptor agonist, CL316,243, but the lipolytic sensitivity to CL316,243 was about 10 times greater than that to isoproterenol in these three adipose tissues. Both isoproterenol and CL316,243 induced more noticeable lipolysis in the epididymal and mesenteric than in the subcutaneous adipose cells in terms of the pD2 value [-log mol l-1 for EC50 (the concentration of an agonist giving half of its own maximum stimulation)]. These findings show that CL316,243 is more lipolytic in the visceral adipose cells than in the subcutaneous adipose cells, although epididymal adipose cells showed a high lipolytic response close to those observed in visceral adipose cells. CL316,243 may therefore be especially useful for the treatment of visceral fat type obesity related to various diseases.

Adipocytes↗
PubMed1997

Octreotide and bromocriptine suppress thyroid hormone levels and thyroid nodule in an acromegalic patient with nontoxic autonomous goiter.

An acromegalic patient with nontoxic autonomous goiter was sequentially treated with octreotide and bromocriptine. Before therapy, serum GH, PRL and insulin-like growth factor-I (IGF-I) levels were increased. Free T3 and free T4 were within the normal range with suppressed TSH levels, whereas 123Iodine-uptake of thyroid was 5.6% after 24 h. During treatment with octreotide and bromocriptine, serum GH, PRL, and IGF-I became normal and free T3 and free T4 were slightly but significantly decreased, but TSH levels remained very low. After thyroidectomy, thyroglobulin, free T3 and free T4 were further decreased, and the TSH levels were recovered to normal. These findings suggested that octreotide and bromocriptine inhibit the release of thyroid hormones from the autonomous thyroid gland directly or indirectly through the decline in IGF-I.

Acromegaly↗
PubMed1997

Anti-obesity and anti-diabetic effects of CL316,243, a highly specific beta 3-adrenoceptor agonist, in Otsuka Long-Evans Tokushima Fatty rats: induction of uncoupling protein and activation of glucose transporter 4 in white fat.

The anti-obesity and anti-diabetic effects of a highly specific beta 3-adrenoceptor agonist, CL316,243 (CL; beta 1: beta 2: beta 3 = 0:1:100,000), were investigated in Otsuka Long-Evans Tokushima Fatty (fatty) and Long-Evans Tokushima Otsuka (control) rats. Daily injection of CL (0.1 mg/kg, s.c.) to these rats (10 weeks old) for 14 weeks caused a significant reduction in body weight (fatty, 27%; control, 15%), associated with a marked decrease in fat pad weight (inguinal: fatty, 60%; control, 36%; retroperitoneal: fatty, 75%; control, 77%) without affecting food intake. The levels of uncoupling protein mRNA and protein levels of uncoupling protein (UCP), as well as guanosine 5'-diphosphate-binding (a reliable index of thermogenesis) in brown adipose tissue, were lower in the fatty than in the control rats. However, after CL treatment, these parameters in brown adipose tissue increased significantly 2- to 3-fold in both groups. Furthermore, uncoupling protein was induced in white adipose tissue as well as in brown adipose tissue. The fatty rats showed hyperglycemia and hyperinsulinemia during the glucose tolerance test, but CL ameliorated these parameters. These findings suggest that decreased thermogenesis in brown adipose tissue may be one of the causes of obesity in the fatty rats and that administration of CL prevents obesity by decreasing white fat mass, by activating brown adipose tissue thermogenesis, and by inducing uncoupling protein in white adipose tissue. Furthermore, CL treatment may inhibit diabetes mellitus by ameliorating obesity and by activating glucose transporter 4 in white adipose tissue and brown adipose tissue.

Adipose Tissue↗
PubMed1997

Effects of Trp64Arg mutation in the beta 3-adrenergic receptor gene on weight loss, body fat distribution, glycemic control, and insulin resistance in obese type 2 diabetic patients.

OBJECTIVE: To investigate the effects of Trp64Arg mutation in the beta 3-adrenergic receptor gene on weight loss, body fat distribution, glycemic control, and insulin resistance in obese type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We measured body weight, waist-to-hip ratio (WHR), adjusted resting metabolic rate, fasting blood glucose, fasting serum insulin levels, insulin resistance index (fasting glucose x fasting insulin/22.5), and HbA1c levels before and after 12 weeks of obesity treatment in 61 obese women with type 2 diabetes. The MvaI polymorphism of the beta 3-adrenergic receptor gene was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: Of obese type 2 diabetic patients, those with the mutation (n = 24) had a higher WHR (P < 0.001), a lower adjusted metabolic rate, and higher blood glucose levels, serum insulin levels, insulin resistance index (P < 0.001), and HbA1c levels (P = 0.016). Furthermore, patients with the mutation had smaller decreases in body weight, WHR, insulin resistance index, and HbA1c levels after the weight-loss program compared with patients without the mutation (n = 37), even though food intake, exercise, and serum thyroid hormone levels were similar in both groups. CONCLUSIONS: These present findings show that the Trp64Arg allele of the beta 3-adrenergic receptor gene may predict difficulty in losing body weight, lowering WHR, and improving glycemic control and insulin resistance in obese patients with type 2 diabetes.

Adult↗
PubMed1997

Beta 3-adrenoreceptor gene polymorphism: a newly identified risk factor for proliferative retinopathy in NIDDM patients.

Proliferative diabetic retinopathy is an important cause of visual impairment. We investigated whether the polymorphism of the beta 3-adrenoreceptor (beta 3-AR) gene, which is associated with insulin resistance and an earlier onset of NIDDM, was associated with proliferative diabetic retinopathy (PDR) in 215 Japanese NIDDM patients with a duration of diabetes of > or = 10 years. The polymorphism of the beta 3-AR gene was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. The Trp64Arg allele of the beta 3-AR gene was significantly more frequent in the NIDDM patients with PDR (P = 0.002), but not in those with non-PDR (P = 0.151), than in NIDDM patients without diabetic retinopathy. Those with the mutation had an earlier onset of diabetes, a longer duration of diabetes, and higher current and maximal BMI values, compared with those without the mutation. Moreover, this mutation was also associated with higher serum triglyceride and decreased HDL-cholesterol levels. When adjustment was made for age, age at diagnosis, duration of diabetes, current BMI, systolic blood pressure, HbA1e, and serum lipids in a multiple regression analysis, a significant association was found between the Trp64Arg allele and diabetic retinopathy (P = 0.039). The Arg/Arg or Arg/Trp genotype was significantly associated with PDR, compared with the Trp/Trp genotype, with an odds ratio of 2.55 (95% CI 1.25-5.16). We concluded that the beta 3-AR gene polymorphism is a newly identified risk factor for PDR.

Aged↗
PubMed1996

Expression of uncoupling protein in skeletal muscle and white fat of obese mice treated with thermogenic beta 3-adrenergic agonist.

The mitochondrial uncoupling protein (UCP) is usually expressed only in brown adipose tissue (BAT) and a key molecule for metabolic thermogenesis. The effects of a highly selective beta 3-adrenergic agonist, CL316,243 (CL), on UCP expression in skeletal muscle and adipose tissues were examined in mice. Daily injection of CL (0.1 mg/kg, sc) to obese yellow KK mice for two weeks caused a significant reduction of body weight, associated with a marked decrease of white fat pad weight and hypertrophy of the interscapular BAT with a sixfold increase in UCP content. Clear signals of UCP protein and mRNA were detected by Western and Northern blot analyses in inguinal, mesenteric and retroperitoneal white fat pads, and also in gastrocnemius and quadriceps muscles, whereas no signal in saline-treated mice. The presence of UCP mRNA in muscle tissues was also confirmed by reverse transcription-PCR analysis. Weaker UCP signals were also detected in control C57BL mice treated with CL, but only in inguinal and retroperitoneal fat pads. Immunohistochemical examinations revealed that UCP stains in the white fat pads were localized on multilocular cells quite similar to typical brown adipocyte, and those in the muscle tissues on myocytes. The mitochondrial localization of UCP in myocytes was confirmed by immunoelectron microscopy. In addition to UCP protein, UCP mRNA was also detected in myocytes by in situ hybridization analysis. Thus, chronic stimulation of the beta 3-adrenergic receptor induces ectopic expression of UCP in adipose tissues conventionally considered as white fat and even in skeletal muscle, which probably contributes to the potent anti-obesity effect of the beta 3-adrenergic agonist.

Adipose Tissue↗
PubMed1996

Effect of CL316,243, a highly specific beta3-adrenoceptor agonist, on sympathetic nervous system activity in mice.

To examine whether long-term administration of a beta3-adrenoceptor agonist influences sympathetic nervous system (SNS) activity, norepinephrine (NE) turnover, a reliable indicator of SNS activity, in the interscapular brown adipose tissue (IBAT), the heart, and the spleen, as well as urinary excretion of NE, were measured using mice treated with CL316,243 (CL), a highly specific beta3-adrenoceptor agonist, at a dose that stimulated thermogenesis and reduced body weight. CL significantly decreased NE turnover in the IBAT, heart, and spleen and decreased urinary excretion of NE without affecting food intake over 1 to 4 weeks of treatment. These findings show that long-term administration of the beta3-adrenoceptor agonist decreases SNS activity and urinary excretion of NE.

Adipose Tissue, Brown↗
PubMed1996

A case of Sheehan's syndrome with delirium.

A 53 year old woman was brought to a psychiatric clinic because of delirium. Upon immediate examination, severe hyponatremia (105 mEq/L) was detected. She was suspected of having internal diseases and referred to our university hospital. When she reached our hospital she was delirious and showed excitement and agitation. Her electroencephalogram showed low voltage theta waves (20 microV) in all leads. She was hospitalized and diagnosed with acute tonsillar abscess and panhypopituitarism based on various endocrine tests. Her past history suggested that Sheehan's syndrome had developed after child-bearing at age 31, resulting in panhypopituitarism. After administration of antibiotics, the fever and tonsillar abscess gradually recovered, and the correction of electrolytes improved the level of consciousness, suggesting that the hyponatremia had been closely related to the clouding of consciousness. As the subsequent administration of cortisol kept the patient's serum sodium levels within the normal range, a decrease in plasma cortisol seemed to be the major cause of the hyponatremia. Psychological symptoms of panhypopituitarism often included abulia, apathy and occasionally coma. However, it is rare for a patient with panhypopituitarism to be misdiagnosed as having a psychiatric disease with delirium. This rare case is presented.

Delirium↗
PubMed1996

Growth hormone (GH) secretory dynamics in a case of acromegalic gigantism associated with hyperprolactinemia: nonpulsatile secretion of GH may induce elevated insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 levels.

We describe a case of pituitary gigantism with low levels of growth hormone (GH), elevated insulin-like growth factor-I (IGF-I), and IGF-binding protein-3 (IGF-BP-3). The patient had characteristic clinical features of gigantism and acromegaly. The basal serum GH levels ranged from 1.2-1.9 micrograms/L, which were considered to be within normal limits. Serum GH response to either insulin-induced hypoglycemia or GH-releasing hormone was blunted. Frequent blood samplings during daytime and at night showed nonpulsatile GH secretion. Serum prolactin, IGF-I and IGF-binding protein-3 levels were elevated. After unsuccessful surgery, bromocryptine treatment normalized serum prolactin without affecting serum GH and IGF-I levels. Combined administration of octreotide and bromocryptine reduced serum GH and IGF-I levels. GH bioactivity as measured by Nb2 cell proliferation assay was within reference range. In the present case, nonpulsatile GH secretion and enhanced tissue sensitivity to GH may induce hypersecretion of IGF-I and IGF-BP-3 and cause clinical acromegalic gigantism.

Acromegaly↗
PubMed1996

Nephrogenic diabetes insipidus induced by lobenzarit disodium treatment in patients with rheumatoid arthritis.

Nephrogenic diabetes insipidus (NDI) occurred in a 43-year-old woman who had received lobenzarit disodium for the treatment of rheumatoid arthritis (RA). Her urine output was initially 3 l/day and urine osmolarity was 203 mOsm/l. Based on a sodium chloride loading test and a vasopressin loading test, she was diagnosed as having lobenzarit-induced NDI. Seven days after the cessation of the use of lobenzarit disodium, polydipsia and polyuria disappeared, and the vasopressin test showed a normal response. These findings suggest that lobenzarit induces a reversible form of NDI as a side effect. The reports of lobenzarit-induced NDI in Japan during the past seven years are also reviewed.

Adult↗