| Project/Area Number |
61440052
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Tokyo Women's Medical College |
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Principal Investigator |
SHIZUME Kazuo Tokyo Women's Medical College, 第二内科, 教授 (40075156)
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| Co-Investigator(Kenkyū-buntansha) |
YASUMOTO Kumiko Tokyo Women's Medical College, 第二内科, 助手 (80151017)
HIZUKA Naomi Tokyo Women's Medical College, 第二内科, 講師 (80147397)
TAKANO Kazue Tokyo Women's Medical College, 第二内科, 助教授 (50096608)
TSUSHIMA Toshio Tokyo Women's Medical College, 第二内科, 教授 (90101089)
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| Project Period (FY) |
1986 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥17,000,000 (Direct Cost: ¥17,000,000)
Fiscal Year 1988: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1987: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1986: ¥10,000,000 (Direct Cost: ¥10,000,000)
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| Keywords | Somatomedin C / IGF-I / IGFーI / インスリン様作用 / 蛋白同化作用 / 成長促進作用 |
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| Research Abstract |
The scarcity of somatomedin/insulin-like growth factor (SM/IGF) has prevented investigation of the mechanism of SM/IGF action. Recently insulin-like growth factor I (IGF-I) has been synthesized by recombinant DNA technology. With the availability of large quantities of the biosynthetic IGF-I, we undertook a study of biological effects of IGF-I in vivo in rats.
120 ug/day of IGF-I was administered continuously for 7 days via s.c. implanted osmotic minipump to hypophysectomized (hypox) and normal rats. The body weights and tibial epiphyseal widths after 7 day treatment of IGF-I in both hypox and normal rats were siginificantly greater than those for untreated rats. These data indicate that IGF-I stimulates growth in vivo not only in GH deficient rats but also in normal rats. Blood urea nitrogen (BUN) levels in both hypox, normal, and diabetic rats treated with IGF-I were significantly lower than those for untrated rats, suggesting that IGF-I has anabolic action in vivo. IGF-I was administ
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ered to fasted rats for 3 days. The reduction of body weight in IGF-I treated rats was smaller than those in untreated fasted rats. The serum and urinary creatin, BUN, and urinary 3-methyl-histidine levels were smaller than those in untreated rats. These data suggest that IGF-I treatment in fasted rats may inhibit the catabolism. IGF-I (100 - 1000) ug/kg BW) was administered as iv bolus to normal and hypox rats. The blood glucose levels decreased after iv bolus injection of the peptide. The effect of IGF-I was 100 times less than that of insulin. Impaired glucose tolerance is often recognized in patients with acromegaly who have high GH levels and high IGF-I levels in plasma. It is not known how the high IGF-I levels plays a role in the glucose metabolism in patients with acromegaly. To understand the pathogenesis, glucose tolerance tests were carried out in ob/ob mice treated with or without IGF-I and hGH. In the mice treated with hGH, the blood glucose levels after administration of glucose were greater than those in untreated mice. However, in the mice treated with IGF-I, the blood glucose levels after glucose load were slightly lower than those in untreated mice. These data suggest that GH itself but not IGF-I may play a role in impaired glucose tolerance in patients with acromegaly.
This study demonstrates that IGF-I has growth promoting, anabolic and insulin-like effects in vivo. Less
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