| Project/Area Number |
11671124
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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 | Ehime University School of Medicine |
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Principal Investigator |
HARUHIKO Osawa Ehime University School of Medicine, Department of Laboratory Medicine Associate Professor, 医学部, 助教授 (90294800)
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| Co-Investigator(Kenkyū-buntansha) |
ONUMA Hiroshi Ehime University School of Medicine, Department of Laboratory Medicine Instructor, 医学部, 助手 (00294794)
MAKINO Hideichi Ehime University School of Medicine, Department of Laboratory Medicine Professor, 医学部, 教授 (50009578)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Phosphodiesterase / insulin resistance / adipocyte differentiation / transcription / promoter / diabetes / adipocyte / gene / インスリン / PDE / 転写因子 |
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| Research Abstract |
Phosphodiesterase (PDE) 3B is activated by insulin, which results in a reduced output of free fatty acids (FFA) from adipocytes. Since an elevation of serum FFA is known to cause insulin resistance, enhanced PDE3B gene expression could improve insulin resistance through reduced serum FFA.We have found that PDE3B gene expression is reduced in adipocytes of obese, insulin-resistant KKAy mice 1). This reduced gene expression is restored by pioglitazone, with concomitant improvement in insulin resistance and elevated serum FFA.PDE3B gene expression is increased upon adipocyte differentiation, which could account for improvement of insulin resistance by peroxisome proliferator-activated receptor (PPAR) γ ligands. To examine the function of PDE3B promoter, we isolated the 5' flanking sequence of mouse PDE3B gene. Analysis of 2kb of this sequence revealed putative binding sites of important transcription factors such as CCAAT enhancer binding protein (C/EBP). The multiple transcription start sites were determined within lk bp upstream from the translation start site. The region including 2 kbp of 5' flanking sequence from the translation start site had promoter activity, which was further activated upon 3T3-L1 adipocyte differentiation. Thus, these isolated mouse PDE3B promoter region could account for its activation upon adipocyte differentiation. Responsible DNA elements for this promoter activation and these binding factors could be good targets of novel insulin sensitizing drugs.
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