2007 Fiscal Year Final Research Report Summary
Study for pathophysiological significance of growth hormone (GH) and insulin-like growth factor in metabolic disorders
| Project/Area Number |
17590968
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
TAKANO Kazue Tokyo Women's Medical University, School of Medicine Department of Medicine II, Professor (50096608)
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| Co-Investigator(Kenkyū-buntansha) |
HIZUKA Naomi Tokyo Women's Medical University, School of Medicine Department of Medicine II, Professor (80147397)
FUKUDA Izumi Tokyo Women's Medical University, School of Medicine Department of Medicine II, Assistant Professor (80238477)
OKUBO Yumiko Tokyo Women's Medical University, School of Medicine Department of Medicine II, Assistant Professor (80287317)
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| Project Period (FY) |
2005 – 2007
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| Keywords | GH / IGF-I / metabolic disorder / adiponectin / adult GH deficiency |
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| Research Abstract |
In this study, we have investigated pathopysiological significance of GH and IGF-I in metabolic disorders as follows.
1) Effect of GH and IGF-I on 11β-hydroxysteroid dehydrogenase typel (HSD1) in 3T3-L1 adipocytes
In peripheral tissues, corticosteroid action is partly regulated by 11β-hydroxysteroid dehydrogenase (11β-HSD) which interconverts hormonally active cortisol (F) and inactive cortisone (E) . The 11β-HSD1 that acts principally as reductase converting E to F, expresses in liver and adipose tissues. Patients with GH deficiency have a clinical feature of visceral adiposity and it has been reported that these patients increased the F/E metabolite ratio. In the present study, we investigated the effect of GH and IGF-I on 11β-HSD1 in 3T3-L1 adipocytes. 3T3-L1 preadipocytes were differentiated to adipocytes according to the conventional method and adipocytes were treated for up to 24 hours with various concentrations of GH or IGF-I. 11β-HSD1 mRNA levels and activity were measured.
… More
11β-HSD1 mRNA levels and activity increased during differentiation from preadipocytes to adipocytes and the levels were suppressed by GH and IGF-I in differentiated adipocytes. These data suggest that 11β-HSD1 activity in adipose tissues is higher with low concentrations of GH and/or IGF-I, leading to an increase in active cortisol that induces adipogenesis and/or lipogenesis. Visceral adiposity in the patients with GH deficiency might be related to increased 11β-HSD1 activity.
2) Serum adiponectin levels and metabolic disorders in the patients with adult GH deficinency
Adiponectin, an adipocyte-derived plasma protein with insulin-sensitizing and anti-atherosclerotic properties, has been found to be a negative regulator of insulin resistance. Patients with adult growth hormone deficiency (GHD) have been found to have increased body fat with abdominal preponderance, prev,alence of premature atherosclerosis, and mortality from cardiovascular disease. It has been suggested that insulin resistance might play some role in these pathogenesis. Adiponectin is found as two forms in serum, as a lower molecular weight (LMW) form and a high molecular weight (HMW) complex. Recently, it has been reported that serum HMW adiponectin correlates better with glucose tolerance than total serum adiponectin. In the present study, we measured serum HMW adiponectin as well as total adiponectin in patients with GHD and investigated the relationship between the adiponectin and insulin resistance in these patients. Serum HMW and total adiponectin levels were measured by ELISA, respectively. Body mass index (BMI) and HOMA-R values in GHD were significantly greater than those in control subjects The median values of serum HMW and total adiponectin levels in patients with GHD were 4.5μg/ml and 8.1μml, respectively. The values were significantly lower than those in controls (5.7μg/ml, 9.9μg/ml). The HMW adiponectin levels inversely correlated with HOMA-R and BMI (Rs=-0.57, Rs=-0.35 ; P<0.01). These data demonstrate that the HMW adiponectin might be related with insulin resistance in patients with GHD. Less
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[Journal Article] Expression of type 5 somatostatin receptor in TSH-secreting pituitary adenomas : A possible marker for predicting long-term response to octreotide therapy2007
Author(s)
Yoshihara, A., Isozaki, O., Hizuka, N., Nozoe, Y., Harada, C., Ono, M., Kawamata, T., Kubo, O., Hon, T., Takano, K
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Journal Title
Endocr J 54
Pages: 133-138
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] KP-102 Study Group : A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency2007
Author(s)
Chihara, K., Shimatsu, A., Hizuka, N., Tanaka, T., Seino, Y., Katofor, Y
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Journal Title
Eur J Endocrinol 157
Pages: 19-27
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Clinical features of insulin-like growth factor-II producing non-islet-cell tumor hypoglycemia2006
Author(s)
Fukuda, I., Hizuka, N., Ishikawa, Y., Yasumoto, K., Murakami, Y., Sata, A., Morita, J., Kurimoto, M., Okubo, Y., Takano, K
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Journal Title
Growth Horm IGF Res 16
Pages: 211-216
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Clinical characteristics, etiologies and pathophysiology of patients with severe short stature with severe GH deficiency : Questionnaire study on the data registered with the Foundation for Growth Science, Japan2006
Author(s)
Hanew, K., Tachibana, K., Yokoya, S., Fujieda, K., Tanaka, T., Igarashi, Y., Shimatsu, A., Tanaka, H., Tanizawa, T., Teramoto, A., Nishi, Y., Hasegawa, Y., Hizuka, N., Hirano, T., Fujita, K
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Journal Title
Endocr J 53
Pages: 259-265
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Effect of growth hormone treatment on trunk fat accumulation in adult OH-deficient Japanese patients : a randomised, placebocontrolled trial2006
Author(s)
Chihara, K., Kato, Y., Takano, K., Shimatsu, A., Kohno, H., Tanaka, T., Irie, M
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Journal Title
Cum Med Res Opin 22
Pages: 1973-1979
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A nationwide attempt to standardize growth hormone assays2005
Author(s)
Tanaka, T., Tachibana, K., Shimatsu, A., Katsumata, N., Tsushima, T., Hizuka, N., Fujieda, K., Yokoya, S., Irie, M
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Journal Title
Horm Res 64 Suppl 2
Pages: 6-11
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Studies of Very Severe Short Stature with Severe GH Deficiency : From the Data Registered with the Foundation for Growth Science2005
Author(s)
Hanew, K., Tachibana, K., Yokoya, S., Fujieda, K., Tanaka, T., Igarashi, Y., Shimatsu, A., Tanaka, H., Tanizawa, T., Teramoto, A., Nishi, Y., Hasegawa, Y., Hizuka, N., Hirano, T., Fujita, K
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Pediatric nonalcoholic steatohepatitis associated with hypopituitarism2005
Author(s)
Nakajima, K., Hashimoto, E., Kaneda, H., Tokushige, K., Shiratori, K., Hizuka, N., Takano, K
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Journal Title
J Gastroenterol 40
Pages: 312-315
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Serum adiponectin levels and insulin resistance in patients with acromegaly2005
Author(s)
Fukuda, I., Hizuka, N., Ishikawa, Y., Morita, J., Kurimoto, M., Murakami, Y., Sata, A., Okubo, Y., Yasumoto, K., Takano, K
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Journal Title
Folia Endocrinologica Japonica (Suppl Sep) 81
Pages: 68-69
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Type I insulin-like growth factor receptor (IGF1R) expression and function in thyroid tissues from a patient with acromegaly2005
Author(s)
Okubo, Y., Kurimoto, M., Kawamata, A., Ishikawa, Y., Isozaki, O., Hizuka, N., Fukuda, I., Obara, T., Takano, K
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Journal Title
Clin Pediatr Endocrinol (Suppl 22) 14
Pages: 37-41
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Clinical features in 78 patients with IGF-II producing non-islet cell tumor hypoglycemia2005
Author(s)
Fukuda, I., Hizuka, N., Ishikawa, Y., Okubo, Y., Murakami, Y., Sata, A., Morita, J., Kurimoto, M., Takano, K
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Journal Title
Folia Endocrinologica Japonica 81(Suppl) 81
Pages: 5-6
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Serum high molecular adiponectin levels and insulin resistance in patients with acromegaly2007
Author(s)
Morita, J., Hizuka, N., Ishikawa, Y., Fukuda, I., Kurimoto, M., Okubo, Y., Takano, K
Organizer
80th Annual Meeting of Japan Endocrine Society
Place of Presentation
Tokyo
Year and Date
2007-06-16
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Changes of serum adiponectin levels in patients with adult GH deficiency during GH treatment2007
Author(s)
Ishikawa, Y., Hizuka, N., Fukuda, I., Kurimoto, M., Morita, J., Sata, A., Murakami, Y., Okubo, Y., Yasumoto, K., Takano, K
Organizer
80th Annual Meeting of Japan Endocrine Society
Place of Presentation
Tokyo
Year and Date
2007-06-15
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Clinical Features of Severe Adult Growth Hormone Deficiency due to The Degree of GH Responsiveness to GHRP-22007
Author(s)
Yamakado, Y., Tanimoto, K., Hizuka, N., Fukuda, I., Kurimoto, M., Yamamoto, M., Takano, K
Organizer
89th Annual Meeting of The Endocrine Society
Place of Presentation
Toronto, Canada
Year and Date
2007-06-02
Description
「研究成果報告書概要(欧文)」より
