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Identification of novel adipocyte-specific factors regulating PDE3B gene transcription different from PPAR_γ

Research Project

Project/Area Number 14571097
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionEhime University

Principal Investigator

OSAWA Haruhiko  Ehime University, School of Medicine, Laboratory medicine, Associate Professor, 医学部, 助教授 (90294800)

Co-Investigator(Kenkyū-buntansha) ONUMA Hiroshi  Ehime University, School of Medicine, Laboratory medicine, Instructor, 医学部, 助手 (00294794)
MAKINO Hideichi  Ehime University, School of Medicine, Laboratory medicine, Professor, 医学部, 教授 (50009578)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsPDE3B / Promoter / Transcription factor / PPAR_γ / Adipocytes / Differentiation / Insulin resistance / diabetes
Research Abstract

Phosphodiesterase 3B(PDE3B) is activated by insulin, which inhibits lipolysis and reduces free fatty acid output from adipocytes. Specific enhancement of PDE3B gene expression could improve insulin resistance. We planned to identify novel adipocyte-specific factors regulating PDE3B gene transcription different from PPAR_γ, by analyzing PDE3B gene promoter lacking PPAR binding sites.
We first constructed 5' deletion promoter reporters starting from the〜2kb length. In parallel, we also found no PPAR binding sites in the human PDE3B gene promoter. We then analyzed the human PDE3B gene promoter. We isolated the 5' flanking region of the PDE3B gene and determined the transcription initiation site by primer extension. We then searched for polymorphisms in this 2kb of the 5' flanking region in 24 type 2 diabetic Japanese subjects using PCR direct sequencing, and the regions including the identified polymorphisms were then examined. Only -465G>T and -1727_-l726insTCAATT had more than 5% frequencies. Since a complete linkage disequilibrium existed between them, -465G>T was further analyzed, along with a previously identified +1389G>A in the coding region in a total of 200 controls and 207 type 2 diabetic subjects. These SNPs and haplotypes were not associated with type 2 diabetes. The T/T genotype at -465 was rare although this frequency could be higher in type 2 diabetes(4/207 subjects) than controls(0/200 subjects). Thus, the identified polymorphisms are unlikely to have major effects on susceptibility to Japanese type 2 diabetes.
We have already constructed human PDE3B gene promoter reporters. We are doing luciferase assays using mouse deletion constructs and human constructs. We are also examining th~ effects of the identified polymorphisms on the protein binding to the DNA elements using electrophoretic mobility shift assays.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Osawa, H. et al.: "Systematic search for single nucleotide polymorphisms (SNPs) in the 5' flanking region of the human phosphodiesterase 3B gene : Absence of evidence for major effects of identified polymorphisms on susceptibility to Japanese type 2 diabetes."Mol Genet Metab. 79. 43-51 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Osawa, H. et al.: "Systematic search for single nucleotide polymorphisms (SNPs) in the FOXC2 gene : The absence of evidence for the association of three frequent SNPs and four common haplotypes with Japanese type 2 diabetes."Diabetes. 52. 562-567 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogura, T. et al.: "Reduction of phosphodiesterase 3B gene expression in peroxisome proliferator-activated receptor γ(+/-) mice independent of adipocyte size."FEBS Lett. 542. 65-68 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Osawa H. et al.: "Systematic search for single nucleotide polymorphisms in the 5' flanking region of the human phosphodiesterase 3B gene : Absence of evidence for major effects of identified polymorphisms on susceptibility to Japanese type 2 diabetes."Mol Genet Metab. 79. 43-51 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Osawa H. et al.: "Systematic search for single nucleotide polymorphisms in the FOXC2 gene : The absence of evidence for the association of three frequent single nucleotide polymorphisms and four common haplotypes with Japanese type 2 diabetes."Diabetes. 52. 562-567 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogura, T. et al.: "Reduction of phosphodiesterase 3B gene expression in peroxisome proliferator-activated receptor γ(+/-) mice independent of adipocyte size."FEBS Lett. 542. 65-68 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Osawa, H.et al.: "Systematic search for single nucleotide polymorphisms (SNPs) in the 5' flanking region of the human phosphodiesterase 3B gene : Absence of evidence for major effects of identified polymorphisms on susceptibility to Japanese type 2 diabetes."Mol Genet Metab. 79. 43-51 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Osawa, H.et al.: "Systematic search for single nucleotide polymorphisms (SNPs) in the FOXC2 gene : The absence of evidence for the association of three frequent SNPs and fourcommon haplotypes with Japanese type 2 diabetes."Diabetes. 52. 562-567 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ogura, T.et al.: "Reduction of phosphodiesterase 3B gene expression in peroxisome proliferator-activated receptor γ (+/-) mice independent of adipocyte size."FEBS Left. 542. 65-68 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Osawa, H. et al.: "Systematic search for single nucleotide polymorphisms (SNPs) in the 5'flanking region of the human phosphodiesierase 3B gene: Absence of evidence for major effects of identified polymorphisms on susceptibility to Japanese type 2 diabetes"Mol Genet Metab. (発売予定). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Osawa, H. et al.: "Systematic search for single nucleotide polymorphisms (SNPs) in the FOXC2 gene: The absence of evidence for the association of three frequent SNPs and four common haplotypes with Japanese type 2 diabetes."Diabetes. 52. 562-567 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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