| Project/Area Number |
10218201
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | UNIVERSITY OF TOKYO |
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Principal Investigator |
FUJITA Toshiro UNIV. OF TOKYO, SCHOOL OF MEDICINE., PROFESSOR, 医学部附属病院, 教授 (10114125)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Katsutoshi UNIV. OF TOKYO, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部附属病院, 助手 (00292863)
TAKANO Koji UNIV. OF TOKYO, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部附属病院, 助手 (20236243)
ANDO Katsuyuki UNIVERSITY OF TOKYO, HEALTH CARE CENTER, LECTURER, 東京大学保健センター, 講師 (60184313)
SHIMOSAWA Tatsuo UNIV. OF TOKYO, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部附属病院, 助手 (90231365)
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| Project Period (FY) |
1998 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥55,300,000 (Direct Cost: ¥55,300,000)
Fiscal Year 2002: ¥11,300,000 (Direct Cost: ¥11,300,000)
Fiscal Year 2001: ¥11,300,000 (Direct Cost: ¥11,300,000)
Fiscal Year 2000: ¥10,900,000 (Direct Cost: ¥10,900,000)
Fiscal Year 1999: ¥10,900,000 (Direct Cost: ¥10,900,000)
Fiscal Year 1998: ¥10,900,000 (Direct Cost: ¥10,900,000)
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| Keywords | vasodilating agent / hypertension / insulin resistance / oxidative stress / knockout mice / organ damage / 心肥大 / 血管障害 / アドレノメデュリン / 高血圧 / 血管平滑筋 |
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| Research Abstract |
Adrenomedullin and PAMP are derived from the same precursor protein and in order to clarify the physiological and therapeutical role of adrenomedullin, we generated adrenomedullin knockout mice by inserting stop mutation in the starting codon of adrenomedullin gene. The homozygous were embryonic lethal and we used heterozygotes. We have reported in 2001 that this mutant showed marked vascular damage by angiotensin II possibly through, overproduction of oxidative stress. In 2002, we demonstrated that aged mutants accumulate oxidative stress and insulin resistance was observed in this aged mutant. Adrenomedullin supplementation or treatment with super oxide dismutase successfully reversed insulin resistant state in the mutants. These results suggest that adrenomedullin is an intrinsic anti-oxidant and its deficiency will cause several oragan damages. Moreover, it will he a new therapeutical agent to prevent complications in common disease such as hypertension, diabetes.
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