Aberrant hepatic TRIB3 gene expression in insulin-resistant obese humans
Aberrant hepatic TRIB3 gene expression in insulin-resistant obese humans
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DOI：
10.1007/s00125-010-1772-2
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发表时间：
2010-09-01
期刊：
影响因子：
8.2
通讯作者：
Patsch, W.
中科院分区：
文献类型：
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作者：
Oberkofler, H.;Pfeifenberger, A.;Patsch, W.
假激酶tribbles同源物3（果蝇）（TRIB 3）负性干扰胰岛素介导的v-akt鼠胸腺瘤病毒癌基因同源物1（AKT 1，也称为蛋白激酶B）的磷酸化和活化。动物研究表明，Trib 3在空腹状态和糖尿病动物模型中的表达更高，可能通过增加肝脏中的葡萄糖产生来促进高血糖症。TRIB 3基因在胰岛素抵抗中的作用目前尚不清楚，但已发现TRIB 3基因存在功能获得性突变，导致胰岛素抵抗相关异常。方法检测TRIB 3基因在肝脏中的mRNA表达，并筛选出与葡萄糖稳态相关的酶、转录因子和辅激活因子基因。我们还确定了具有不同程度胰岛素抵抗的肥胖患者中间代谢的生化变量。结果在我们的研究人群中，肝脏TRIB 3 mRNA表达与胰岛素抵抗的替代标志物相关。与低HOMA-IR组相比，具有高HOMA-IR的胰岛素抵抗（HOMA-IR）亚组中TRIB 3表达显著增加（p=0.0033）。TRIB 3转录水平与PEPCK（也称为PCK 2）mRNA表达（p=0.0014）和PPARGC 1A（p=0.0020）、PPARGC 1B（p= 0.0014）mRNA表达相关。
Aims/hypothesis The pseudokinase tribbles homologue 3 (Drosophila) (TRIB3) negatively interferes with insulin-mediated phosphorylation and activation of v-akt murine thymoma viral oncogene homologue 1 (AKT1, also known as protein kinase B). Animal studies have shown that Trib3 expression was higher in the fasting state and in animal models of diabetes, promoting hyperglycaemia presumably by increasing glucose production in the liver. Less is known about the role of TRIB3 in insulin resistance in humans, although a gain-of-function mutation associated with abnormalities related to insulin resistance has been described in TRIB3.Methods We determined hepatic mRNA expression of TRIB3 and selected genes encoding enzymes, transcription factors and coactivators involved in glucose homeostasis. We also determined biochemical variables of intermediary metabolism in obese patients with varying degrees of insulin resistance.Results In our study population hepatic TRIB3 mRNA expression was associated with surrogate markers of insulin resistance. TRIB3 expression was significantly increased in a subgroup with high HOMA of insulin resistance (HOMA-IR) compared with a low HOMA-IR group (p=0.0033). TRIB3 transcript levels were correlated with PEPCK (also known as PCK2) mRNA expression (p=0.0014) and mRNA expression of PPARGC1A (p=0.0020), PPARGC1B (p