Identification of transcription activators of resistin gene with type 2 diabetes susceptibility promoter SNP

2型糖尿病易感性启动子SNP抵抗素基因转录激活子的鉴定

基本信息

  • 批准号:
    17590938
  • 负责人:
  • 金额:
    $ 2.24万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2005
  • 资助国家:
    日本
  • 起止时间:
    2005 至 2006
  • 项目状态:
    已结题

项目摘要

Resistin, secreted from adipocytes, causes insulin resistance in rodents. In humans, the main source of resistin is thought to be monocytes, and its pathophysiological relevance has been controversial. We previously reported that the G/G genotype of a resistin gene promoter single nucleotide polymorphism (SNP) at-420 increases-type 2 diabetes (T2DM) susceptibility by enhancing promoter activity. We also found that circulating resistin was associated with the G allele number of SNP-420, and correlated with insulin resistance. To identify targets of insulin sensitizing drugs specifically affecting the resistin gene promoter including T2DM susceptibility allele, G at SNP-420, we analyzed the mechanism of resistin gene expression in THP-1 human monocytes.. We made luciferase reporters including different length of 5' flanking region of the human resistin gene with either C or G at SNP-420. We found that the 5' flanking region had the promoter activities. We also analyzed effects of hormone … More s and drugs on resistin mRNA in THP-1 cells. Some molecules affected resistin mRNA in a dose and time dependent manner. However, these molecules did not affect resistin promoter activities. We did not detect resistin protein in cell lysate and cultured medium in THP-1 cells. Therefore, resistin gene expression could be most sensitively assessed by analyzing its mRNA in THP-1 cells. In freshly isolated human monocytes, resistin mRNA was positively correlated with its simultaneous serum levels, and highest in G/G genotype. In T2DM, serum resistin was higher in subjects with advanced microangiopathies. These findings suggest that resistin mRNA in human monocytes is associated with SNP-420, which is correlated with serum resistin, and that serum resistin is higher in T2DM, especially with advanced microangiopathies. Therefore, the identification of agents reducing resistin gene transcription or mRNA in monocytes could prevent the development of T2DM and the progression of its complications. Less
抵抗素,由脂肪细胞分泌,导致啮齿类动物的胰岛素抵抗。在人类中,主要来源的BLORN被认为是单核细胞,其病理生理学相关性一直存在争议。我们以前报道过,G/G基因型在-420位点的单核苷酸多态性(SNP)通过增强启动子活性增加2型糖尿病(T2 DM)的易感性。我们还发现循环中的Gln与SNP-420的G等位基因数量相关,并与胰岛素抵抗相关。为了确定胰岛素增敏药物特异性影响T2 DM易感性等位基因GSNP-420的靶点,我们分析了THP-1人单核细胞中T2 DM易感性等位基因GSNP-420的表达机制。我们制备了荧光素酶报告基因,其包括不同长度的人Glycogen基因的5'侧翼区,在SNP-420处具有C或G。我们发现5'侧翼区具有启动子活性。我们还分析了激素的作用 ...更多信息 S和药物对THP-1细胞中BMPN mRNA的影响。有些分子以剂量和时间依赖性方式影响BcnmRNA。然而,这些分子并不影响cDNAn启动子活性。在THP-1细胞的细胞裂解液和培养液中均未检测到cDNAn蛋白。因此,通过分析THP-1细胞中的mRNA,可以最灵敏地评估BMPn基因表达。在新鲜分离的人单核细胞中,gene mRNA与其同时血清水平呈正相关,且在G/G基因型中最高。在T2 DM中,晚期微血管病变受试者的血清β-淀粉样蛋白较高。这些发现表明,人单核细胞中的β-内酰胺酶mRNA与SNP-420相关,SNP-420与血清β-内酰胺酶相关,并且血清β-内酰胺酶在T2 DM中更高,特别是在晚期微血管病变中。因此,鉴定降低单核细胞中的GSTN基因转录或mRNA的药物可以预防T2 DM的发展及其并发症的进展。少

项目成果

期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Resistin SNP-420 determines its monocyte mRNA and serum levels inducing type 2 diabetes
Serum resistin is associated with the severity of microangiopathies in type 2 diabetes
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OSAWA Haruhiko其他文献

OSAWA Haruhiko的其他文献

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{{ truncateString('OSAWA Haruhiko', 18)}}的其他基金

Epigenetic models of insulin resistance targeting the human resistin gene
针对人类抵抗素基因的胰岛素抵抗的表观遗传模型
  • 批准号:
    21591141
  • 财政年份:
    2009
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Application of Resistin SNP to Order-made Medicine of Metabolic Syndrome
抵抗素SNP在代谢综合征定制药物中的应用
  • 批准号:
    19591055
  • 财政年份:
    2007
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Identification of novel adipocyte-specific factors regulating PDE3B gene transcription different from PPAR_γ
鉴定不同于 PPAR_γ 的新型脂肪细胞特异性调节 PDE3B 基因转录的因子
  • 批准号:
    14571097
  • 财政年份:
    2002
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

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