| Project/Area Number |
15390286
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 (2004) Kyoto University, Graduate school of Medicine, Lecturer, 医学研究科, 講師 (50343231)
清野 裕 (2003) 京都大学, 医学研究科, 教授 (40030986)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Yuichiro Kyoto University, Graduate school of Medicine, Associate Professor, 医学研究科, 助教授 (60283610)
細川 雅也 京都大学, 医学研究科, 講師 (50343231)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2004: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 2003: ¥9,200,000 (Direct Cost: ¥9,200,000)
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| Keywords | incretin / GIP / GLP-1 / pancreatic beta cells / adipocyte / osteoblast |
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| Research Abstract |
In the current study, we investigated the molecular mechanism to secrete incretin-the functional linkage between nutrient and gut function-.
We also investigated how incretin regulate the metabolism-functional relationship between gut and various organs-. And we speculated the role of gut signal in whole body.
There exists a splicing variant of GIP receptor in pancreatic beta cells and the variant act on GIP receptor in a dominant-negative fashion. Thus we clarified a part of mechanism of insufficiency of GIP action. The double deficient mouse of GIP receptor and GLP-1 receptor have short and thin bones. This attributed partly to the inhibition of the activity of osteoblast by GIP and GLP-1, and partly to promotion of the activity of osteoblast by by GIP and GLP-1. And GIP inhibited apotosis in a cell line osteoblast dose-dependently. We generated a transgenic mice which re-expressed GIP receptor only in adopocyte. We confirmed that the mice the re-expressed of GIP receptor in adipocyte and deficiency of GIP receptor in other tissues. On the other hand, we generated the double deficient mice of both GIP receptor and IRS-1 to gain more insight to the relationship between GIP receptor and adipocyte. In the double deficient mice, the deficiency of GIP signal improved the insulin resistance in liver by means of increment of beta-oxidation of fatty acid. And we demonstrated the molecular mechanism of the improvement is based on the upregulation of the gene expression of UCP-2 and FAT. And the gene of HD, CPT-1, and ACX did not involve in the improvement of insulin resistance.
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