4.4 Article

Identification of a functional protein kinase Cβ promoter polymorphism in humans related to insulin resistance

期刊

MOLECULAR GENETICS AND METABOLISM
卷 93, 期 2, 页码 210-215

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymgme.2007.09.004

关键词

protein kinase c; insulin resistance; HOMA-IR; insulin; diabetes; promoter polymorphism

向作者/读者索取更多资源

Protein kinase CP (PKC beta) is known to inhibit insulin production in beta-cells and to support insulin action in skeletal muscle. We therefore searched for functional polymorphisms among already known genetic variants in the PKC beta promoter and investigated their relation to glucose metabolism in humans. We found that the gene variant in the PKC13 promoter at position -546 significantly reduced promoter activity in functional assays (P < 0.05). Human subjects carrying this variant had a 3.5-fold decrease in PKC beta 2-protein expression in their thrombocytes (P = 0.006). Additionally, we tested whether this variant affects parameters of glucose metabolism using 1012 humans included into the MeSyBePo study (Metabolic Syndrome Berlin Potsdam). The -546 variant was highly significant associated with increased homeostasis model assessment for insulin resistance (HOMA-IR, P = 0.009) in the cohort. This association was accompanied by significantly increased fasting insulin concentrations in carriers of the homozygous polymorphism (P = 0.021). Our results suggest that the -546 polyrnorphism in the PKC beta promoter reduces promoter activity, which leads to a decreased expression of PKC beta 2 and subsequently is associated with decreased peripheral insulin-dependent glucose uptake. (C) 2007 Elsevier Inc. All rights reserved.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.4
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据