2006 Fiscal Year Final Research Report Summary
Identification of transcription activators of resistin gene with type 2 diabetes susceptibility promoter SNP
| Project/Area Number |
17590938
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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 |
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Principal Investigator |
OSAWA Haruhiko Ehime University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (90294800)
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| Co-Investigator(Kenkyū-buntansha) |
MAKINO Hideichi Ehime University, Graduate School of Medicine, Proffesor, 大学院・医学系研究科, 教授 (50009578)
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| Project Period (FY) |
2005 – 2006
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| Keywords | resistin / adipocytes / promoter / diabetes / insulin resistance / monocytes / gene expression / cytokine |
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| Research Abstract |
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
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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
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Research Products
(4 results)
