| Project/Area Number |
13671188
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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 |
Metabolomics
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| Research Institution | Kyoto University |
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Principal Investigator |
HOSOKAWA Masaya (2002) Medicine, Diabetes and clinical nutrition, lecturer, 医学研究科, 講師 (50343231)
黒瀬 健 (2001) 京都大学, 医学研究科, 講師 (90264374)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Yuichiro Medicine, Diabetes and clinical nutrition, assistant professor, 医学研究科, 助教授 (60283610)
井原 裕 岡山県立大学, 保健福祉学部, 助教授 (50322160)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | circadian clock / insulin secretion / 時計遺伝子 / 膵内分泌 / インスリン / CLOCK / BMAL-1 / CRY1 / CRY2 / ノックアウトマウス |
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| Research Abstract |
The cry1 and cry2 are circadian clock associated-genes. The double knockout mouse (cry1^% cry2^% mouse) exhibited tbe impaired glucose tolerance in oral glucose tolerance test at the time point of 15 min, 30min, and 60 min when compared to wild type. However, at 90 min and 120 min, the levels of blood glucose of the double knockout mouse were similar to those of wild type. In order to confirm the phenomenon at cellular level, we have isolated pancreatic islets by collagenase digestion, and did batch incubation. The insulin response of the double knockout islets to 8.3 and 16.7 mM glucose reduce by 50% when compared to wild type. Furthermore in the experiment of pancreatic perfusion, the first phase response of insulin to 16.7 mM glucose reduce by 50% when compared to wild type. Yet the second phase response was similar to those of wild type. In insulin tolerance test, the double knockout mouse exhibited the better insulin sensitivity when compared to wild type, suggesting the possibility that the hypersensitivity may account for the normal return of blood glucose level 120 min after oral glucose loading. Histopathological examination revealed the hypertrophy of pancreatic islets of the double knockout mouse. Besides the double knockout mouse exhibited physical retardation , but the amount of food intake are indistinguishable with wild type. We concluded that cry1 and cry2 regulate the early insulin secretion in response to glucose stimulation and may regulate growth-hormone secretion or bone metabolism
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