| Project/Area Number |
09835022
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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 |
老化(加齢)
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| Research Institution | Tokyo Metropolitan Institute of Gerontology |
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Principal Investigator |
OHTA Minoru Tokyo Metro. Inst. Gerontol. Assistant Researcher of Dept. Clin Physiol., 臨床生理部門, 研究助手 (70133634)
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| Co-Investigator(Kenkyū-buntansha) |
MIYASAKA Kyoko Tokyo Metro. Inst. Gerontol. Head of Dept. Clin Physiol., 臨床生理部門, 研究室長 (90166140)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | behavior / CCK / CCK receptor / CCK-A receptor / CCK-B receptor / gene / obesity / diabetes mellitus / CCK-A受容体 / コレシストキニン / CCK-A受容体遺伝子欠損 / ノックアウト / 行動異常 / コレシストキニン(CCK) / CCK-A-受容体 / NIDDM / LTP |
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| Research Abstract |
We found that OLETF rats, an inbred strain of spontaneous mutants, which develop persistent hyperglycemia and mild obesity, did not express CCK-A receptor gene because of a genetic abnormality. The rat CCK-A receptor gene is -10kb long and consists of five exons interrupted by four introns, and two exons are deleted in OLETF rats. OLETF rats revealed several abnormal functions possible due to a defect of the CCK-A receptor including hyperphagia, decrease in exploratory behavior, impaired response of insulin and pancreatic enzyme secretion, and retardation of pancreatic growth and regeneration. In the present study, we found additional observations. The diurnal rhythm of energy expenditure was flattened after 24 weeks of age in OLETF rats. The transport of lipid from the small intestinal mucosa into the lymph was enhanced at 18 weeks of age and this enhancement was improved by the prevention of obesity. The lymphocyte subpolulation after restriction stress was not changed. The dopamine release from the striatum was not different from the control LETO rats by microanalysis. The imaging of striatum by PET was also comparable for both strains. In order to determine the role of CCK-A receptor gene knockout mice. The mice are fertile and show normal growth. Gallstone formation was observed at 65 weeks of age in 3 of 4 CCK-A receptor (-/-) mice, whereas no gallstone formation was observed in (+/-) and (+/+) mice.
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