Impaired miR-146a expression links subclinical inflammation and insulin resistance in Type 2 diabetes
Impaired miR-146a expression links subclinical inflammation and insulin resistance in Type 2 diabetes
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DOI：
10.1007/s11010-011-0727-3
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发表时间：
2011-05-01
影响因子：
4.3
通讯作者：
Mohan, V.
中科院分区：
文献类型：
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作者：
Balasubramanyam, M.;Aravind, S.;Mohan, V.
2型糖尿病患者表现出亚临床炎症，但其调控机制尚不清楚。我们试图评估miR-146 a表达沿着其下游促炎信号在血糖控制和胰岛素抵抗中的作用。研究受试者（各n = 20）包括临床特征良好的2型糖尿病患者和对照非糖尿病受试者。通过实时RT-PCR检测外周血单个核细胞（PBMC）中的miRNA和mRNA表达水平，并通过ELISA测量TNF α和IL-6的血浆水平。与对照受试者相比，2型糖尿病患者PBMC中的miR-146 a表达水平显着降低。在miR-146 a靶基因中，TRAF-6 mRNA在2型糖尿病患者中表达显著增加，而IRAK 1 mRNA在研究组中的表达水平无显著差异。相反，2型糖尿病患者NF κ B B表达水平显著升高。2型糖尿病患者TNF α和IL-6 mRNA水平有升高趋势。在2型糖尿病患者中，SOCS-3 mRNA水平升高，血浆TNF α和IL-6水平也显著升高。miR-146 a表达与糖化血红蛋白、胰岛素抵抗、TRAF 6和NF κ B B mRNA水平以及TNF α和IL-6的循环水平呈负相关。miR-146 a水平降低与亚洲印度2型糖尿病患者的胰岛素抵抗、血糖控制不良、几种促炎细胞因子基因和TNF α和IL-6循环水平相关。
Type 2 diabetes patients exhibit subclinical inflammation but the regulatory mechanisms are poorly understood. We sought to evaluate the role of miR-146a expression along with its downstream proinflammatory signals in relation to glycemic control and insulin resistance. Study subjects (n = 20 each) comprised of clinically well characterized Type 2 diabetes patients and control non-diabetic subjects. miRNA and mRNA expression levels were probed in peripheral blood mononuclear cells (PBMC) by Real-time RT-PCR and plasma levels of TNF alpha and IL-6 were measured by ELISA. The miR-146a expression levels were significantly decreased in PBMCs from patients with Type 2 diabetes compared to control subjects. Among the target genes of miR-146a, TRAF-6 mRNA expression was significantly increased in patients with Type 2 diabetes while there was no significant difference in the mRNA levels of IRAK1 in the study groups. In contrast, there were significantly increased levels of NF kappa B expression in patients with Type 2 diabetes. There was an increased trend in the levels of TNF alpha and IL-6 mRNA in patients with type 2 diabetes. While SOCS-3 mRNA levels increased, plasma TNF alpha and IL-6 levels were also significantly higher in patients with type 2 diabetes. miR-146a expression was negatively correlated to glycated hemoglobin, insulin resistance, TRAF6, and NF kappa B mRNA levels and circulatory levels of TNF alpha and IL-6. Reduced miR-146a levels are associated with insulin resistance, poor glycemic control, and several proinflammatory cytokine genes and circulatory levels of TNF alpha and IL-6 in Asian Indian Type 2 diabetic patients.