Endocrine Journal
Online ISSN : 1348-4540
Print ISSN : 0918-8959
ISSN-L : 0918-8959
Volume 58 , Issue 3
Showing 1-10 articles out of 10 articles from the selected issue
REVIEW
ORIGINALS
  • Sumito Dateki, Maki Fukami, Yoko Tanaka, Goro Sasaki, Hiroyuki Moriuch ...
    2011 Volume 58 Issue 3 Pages 155-159
    Published: 2011
    Released: March 31, 2011
    [Advance publication] Released: January 14, 2011
    JOURNALS FREE ACCESS
    We report a de novo heterozygous 5,013,940 bp terminal deletion of chromosome 15q26 in a 13 9/12 -year-old Japanese girl with short stature (-3.9 SD), mild mental retardation, and ventricular septal defect (VSD). This terminal deletion involved IGF1R but not NR2F2, and was associated with an addition of telomere repeat sequences (TTAGGG) at the end of the truncated chromosome. The results provide further support for the notion that terminal deletions are healed by de novo addition of telomere sequences essential for chromosome stability and DNA replication. Furthermore, while growth failure and mental retardation are primarily explained by loss of IGF1R, the occurrence of VSD might suggest the existence of a cardiac anomaly gene, other than the candidate cardiac anomaly gene NR2F2, in the deleted region.
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  • Mie Arakawa, Takayuki Masaki, Junko Nishimura, Masataka Seike, Hironob ...
    2011 Volume 58 Issue 3 Pages 161-170
    Published: 2011
    Released: March 31, 2011
    [Advance publication] Released: March 01, 2011
    JOURNALS FREE ACCESS
    It has been demonstrated the involvement of branched-chain amino acids (BCAA) on obesity and related metabolic disorder. We investigated the effects of branched-chain amino acids (BCAA) on obesity and on glucose/fat homeostasis in mice fed on a high-fat (45%) diet. BCAA was dissolved in 0.5% methylcellulose and added to the drinking water (BCAA-treated group). A high-fat diet was provided for 6 weeks and BCAA was given for 2 weeks. The BCAA-treated group gained almost 7% less body weight and had less epididymal adipose tissue (WAT) mass than the control group (p<0.05). BCAA supplementation also reduced the hepatic and skeletal muscle triglyceride (TG) concentrations (p<0.05). The hepatic levels of PPAR-alpha and uncoupling protein (UCP) 2, and the level of PPAR-alpha and UCP3 in the skeletal muscle were greater in the BCAA-treated group than in the control mice (p<0.05). These results demonstrate that the liver and muscle TG concentration are less in BCAA-treated group. BCAA affects PPAR-alpha and UCP expression in muscle and liver tissue.
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  • Yoshiaki Kawagoe, Yoshiyuki Hattori, Ayuko Nakano, Chie Aoki, Seiichi ...
    2011 Volume 58 Issue 3 Pages 171-175
    Published: 2011
    Released: March 31, 2011
    [Advance publication] Released: February 04, 2011
    JOURNALS FREE ACCESS
    It is well established that statins improve the prognosis of patients with coronary artery disease. However, it is still unclear whether the protective effects of statins relate to lipid lowering alone or whether other pleiotropic effects may contribute. Thus, we compared the endothelial function among two groups of diabetic patients treated with fluvastatin 60 mg (F60) or fluvastatin 20 mg combined with ezetimibe 10 mg (F20/E10). The endothelial function was evaluated by measuring flow-mediated vasodilatation (FMD) at baseline and follow-up at 10 weeks. Similar improvements in FMD were observed in the two groups. The reduction in low-density lipoprotein cholesterol (LDL-C) was less pronounced in the F60 group, compared with the F20/E10 group. A significant reduction in remnant-like lipoprotein particles cholesterol (RLP-C) was observed in the F20/E10 group, but not in the F60 group. A correlation between the observed reduction in LDL-C or RLP-C and the improvement in FMD was observed in F20/E10 group. These results suggest that high-dose fluvastatin might have pleiotropic effects of potential clinical benefit, and that the combination of ezetimibe with a reduced dose of fluvastatin may also significantly improve endothelial function with reduction of LDL-C and RLP-C.
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  • Yu Cheng, Ying Xiang, Youzhi Lin, Songbin Fu, Wenzhi Jia, Guanghui Zha ...
    2011 Volume 58 Issue 3 Pages 177-184
    Published: 2011
    Released: March 31, 2011
    [Advance publication] Released: February 22, 2011
    JOURNALS FREE ACCESS
    The purpose of this study was to investigate the role of retinoic acid (RA) and/or dexamethasone and growth hormone releasing hormone (GHRH) in the induction of somatotroph cell differentiation. Immunohistochemistry, radioimmunoassay, 3-(4,5-dimethylthiazol -1,2-y1)-2,5-diphenyltetrazolium bromide assay, and immune electron microscopy were employed to determine the effect of incubation with these constituents on the differentiation into somatotrophs of cells isolated from the rat embryonic pituitary gland. RA administration increased the proportion of growth hormone (GH) positive somatotroph cells and GH secretion in embryonic pituitary cells (P<0.01). After 4 days of incubation with RA, additional administration of dexamethasone further increased the proportion of somatotroph cells and GH secretion (P<0.01), and increased the number of secretory granules in the somatotroph cells. Addition of GHRH alone had no such effect (P>0.05). However, addition of GHRH to treatment with RA plus dexamethasone significantly increased both the proportion of somatotroph cells and the secretion of GH compared to treatment with RA or dexamethasone alone or RA plus dexamethasone (P<0.01). RA promoted the early differentiation of somatotroph cells, dexamethasone promoted the differentiation and maturation of somatotroph cells and in addition, RA, dexamethasone and GHRH together exerted synergistic effects that markedly promoted somatotroph cell differentiation, maturation and GH secretion.
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  • Tadashi Yamakawa, Takeshi Kaneko, Erina Shigematu, Junko Kawaguchi, Ka ...
    2011 Volume 58 Issue 3 Pages 185-191
    Published: 2011
    Released: March 31, 2011
    [Advance publication] Released: February 22, 2011
    JOURNALS FREE ACCESS
    We previously reported that colestimide, an anion exchange resin, improved glycemic control in patients with type 2 diabetes. However, the factors associated with the decrease of HbA1c remain unclear. In present study, we retrospectively compared glycemic control between groups receiving colestimide (n=71), atorvastatin (n=99), pravastatin (n=85), and pitavastatin (n=95) until 3 months after the start of treatment. In the colestimide group, fasting plasma glucose decreased significantly from 169 ± 59 to 138 ± 29 mg/dL after 3 months (P<0.01), and glycated hemoglobin (HbA1c) declined from 8.1 ± 1.0% to 7.4 ± 0.8% (an 8% reduction, P<0.01). Fasting plasma glucose and HbA1c did not change in the pravastatin and pitavastatin groups. On the other hand, both parameters increased significantly in the atorvastatin group. Multivariate analysis revealed that baseline HbA1c was the main determinant of the decrease of HbA1c in the colestimide group while age, sex, BMI, and baseline lipid levels were not correlated with the effect of colestimide treatment. The decrease of HbA1c showed a positive correlation with baseline HbA1c (r=0.60, P<0.0001), and patients with a larger change of HbA1c (>8.4%) displayed a better response to colestimide. In conclusion, since patients with type 2 diabetes often have hyperlipidemia as well, colestimide therapy may have a clinically useful dual action in such patients. Baseline HbA1c has the most important independent influence on the glucose-lowering effect of colestimide.
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  • Keiji Tanimoto, Saori Onda, Hideaki Sawaki, Tetsuya Hiraiwa, Hiroyuki ...
    2011 Volume 58 Issue 3 Pages 193-198
    Published: 2011
    Released: March 31, 2011
    [Advance publication] Released: February 17, 2011
    JOURNALS FREE ACCESS
    We report a 21-year-old man with severe fatigue due to hypopituitarism. At the age of 6 years, he was diagnosed with short stature due to a GH deficiency accompanied by a sphenoid cystic lesion. Laboratory findings and provocative tests for pituitary hormone function revealed ACTH, LH, FSH, TSH, and GH deficiency. Computed tomography and magnetic resonance imaging revealed transsphenoidal cephalocele due to a defect in the floor of the sella turcica. At 6 years, he only had severe GH deficiency and poor response of LH to LHRH. Hypothalamic-pituitary dysfunction and pituitary herniation have progressed subsequently; we observed a longitudinal progression of hypothalamic-pituitary dysfunction caused by transsphenoidal cephalocele. This dysfunction requires the selection of a treatment that will not aggravate the condition further.
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  • Juan Liu, Long Wang, Aisen Zhang, Wenjuan Di, Xiao Zhang, Lin Wu, Jing ...
    2011 Volume 58 Issue 3 Pages 199-209
    Published: 2011
    Released: March 31, 2011
    [Advance publication] Released: February 17, 2011
    JOURNALS FREE ACCESS
    Current pharmacological treatments for obesity and metabolic syndrome have various limitations. Recently, adipose tissue 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) has been proposed as a novel therapeutic target for the treatment of obesity and metabolic syndrome. Nevertheless, there is no adipose tissue-targeted 11β-HSD1 inhibitor available now. We sought to develop a new 11β-HSD1 pharmacological inhibitor that homes specifically to the white adipose tissue and aimed to investigate whether adipose tissue-targeted 11β-HSD1 inhibitor might decrease body weight gain and improve glucose tolerance in diet-induced obesity mice. BVT.2733, an 11β-HSD1 selective inhibitor was connected with a peptide CKGGRAKDC that homes to white fat vasculature. CKGGRAKDC-BVT.2733 (T-BVT) or an equimolar mixture of CKGGRAKDC and BVT.2733 (NT-BVT) was given to diet-induced obesity mice for two weeks through subcutaneous injection. T-BVT decreased body weight gain, improved glucose tolerance and decreased adipocyte size compared with vehicle treated mice. In adipose tissue T-BVT administration significantly increased adiponectin, vaspin mRNA levels; In liver T-BVT administration decreased the mRNA level of phosphoenolpyruvate carboxykinase (PEPCK), increased the mRNA levels of mitochondrial carnitine palmi-toyltransferase-I (mCPT-I) and peroxisome proliferator-activated receptorα(PPARα). No significant differences in adipocyte size and hepatic gene expression were observed after treatment with NT-BVT compared with vehicle treated mice, though NT-BVT also decreased body weight gain, improved glucose tolerance, and increased uncoupling protein-2 (UCP-2) mRNA levels in muscle. These results suggest that an adipose tissue-targeted pharmacological inhibitor of 11β-HSD1 may prove to be a new approach for the treatment of obesity and metabolic syndrome.
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NOTES
  • Yoshiaki Tamura, Keiichi Watanabe, Tomomi Kantani, Junichi Hayashi, No ...
    2011 Volume 58 Issue 3 Pages 211-215
    Published: 2011
    Released: March 31, 2011
    [Advance publication] Released: February 05, 2011
    JOURNALS FREE ACCESS
    The beneficial effects of endurance exercise include insulin-sensitization and reduction of fat mass. Limited knowledge is available about the mechanisms by which endurance exercise exerts the salutary effects. Myokines, cytokines secreted by skeletal muscle, have been recognized as a potential mediator. Recently, a role of skeletal muscle-derived interleukin-15 (IL-15) in improvement of fat-lean body mass composition and insulin sensitivity has been proposed. Yet, previous studies have reported that endurance training does not increase production or secretion of IL-15 in skeletal muscle. Here, we show that in opposition to previous findings, 30-min treadmill running at 70% of age-predicted maximum heart rate resulted in a significant increase in circulating IL-15 level in untrained healthy young men. These findings suggest that IL-15 might play a role in the systemic anti-obesogenic and insulin-sensitizing effects of endurance exercise, not only as a paracrine and autocrine but also as an endocrine factor.
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  • Takumi Kudo, Akira Miyauchi, Yasuhiro Ito, Tomonori Yabuta, Hiroyuki I ...
    2011 Volume 58 Issue 3 Pages 217-221
    Published: 2011
    Released: March 31, 2011
    [Advance publication] Released: February 24, 2011
    JOURNALS FREE ACCESS
    Calcitonin is a very sensitive tumor marker of medullary thyroid carcinoma (MTC). Patients with MTC have usually very high levels of serum calcitonin that can be used to diagnose the disease. In order to improve diagnostic sensitivity in family members with small MTCs or to evaluate postoperative biochemical cure status, measurement of calcitonin stimulated with combined intravenous calcium gluconate and pentagastrin has been widely adopted; however, gastrin has become unavailable. Currently, a provocative test using only calcium gluconate is performed; however, the standard values for this test have not been reported. We therefore conducted calcium gluconate stimulation tests in 20 patients before and after total thyroidectomy for thyroid diseases other than MTC. Preoperatively, the mean basal calcitonin level was 24.1 pg/mL and increased to 46.9pg/mL after calcium infusion. The ratio of the peak calcitonin level to the basal value ranged from 1- to 5.23-fold, with a mean of 1.94. The ratio was higher than 3-fold in 3 patients. In 2 patients, peak calcitonin levels exceeded 100 pg/mL. Postoperatively, the mean basal level slightly decreased to 21.15pg/mL and the response to calcium stimulation markedly decreased, with the mean ratio decreasing to 1.1-fold (range, 0.86- to 1.73-fold, maximum peak level, 33 pg/mL). Thus, some subjects without MTC show response to the calcium stimulation test up to 5.24 times the ratio and a peak value of 160 pg/mL, suggesting the requirement for judicious judgment for the early diagnosis of MTC in family members; however, after total thyroidectomy, none of the subjects showed an increase of more than 2-fold or a peak value of 33pg/mL, suggesting that responses greater than 2-fold after MTC surgery might be abnormal, indicating the presence of residual tumor.
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