| 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)
村上 祐子 東京女子医科大学, 医学部, 助手 (60318029)
佐田 晶 東京女子医科大学, 医学部, 助手 (60360153)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,710,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | GH / IGF-I / metabolic disorder / adiponectin / adult GH deficiency / 11βHSD1 / メタボリック症候群 / IGF / NAFLD / NASH / GH分泌不全症 / 先端巨大症 / 11βHSD / アディポサイトカイン |
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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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