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诱导性糖尿病前期和2型糖尿病大鼠外周血单个核细胞中miR-103和miR-143表达失调。

Dysregulated miR-103 and miR-143 expression in peripheral blood mononuclear cells from induced prediabetes and type 2 diabetes rats.

作者信息

Vatandoost Nasimeh, Amini Masoud, Iraj Bijan, Momenzadeh Sedigheh, Salehi Rasoul

机构信息

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Isfahan Endocrine and Metabolic Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

Gene. 2015 Nov 1;572(1):95-100. doi: 10.1016/j.gene.2015.07.015. Epub 2015 Jul 8.

Abstract

The progression from normal glucose tolerance (NGT) to type 2 diabetes (T2D) occurs through an intermediate state of glucose intolerance known as pre-diabetes. This transition is usually a gradual phenomenon that occurs over 5-10 years. Among the routinely practiced T2D screening criteria, like, FPG, IFG, IGT or HbA1c, still the issue of a preferable one is debated. The newly emerged microRNAs are created much hope to act as a class of suitable diabetes gene signature detectable at an early stage of the disease development. Although T2D related miRNA fluctuations are reported from the main insulin target organs, sampling of these organs for the sake of screening due to its invasive nature is not practicable. Peripheral blood mononuclear cells (PBMCs) are in constant touch with all body organs hence may exhibit the trace of miRNA changes which take place in insulin target organs. In this study we have evaluated miR-103 and miR-143 expression in three groups of rats namely; normal control, high fat diet (HFD) which is corresponding to prediabetes state, and high fat diet/streptozotocin (STZ) induced T2D. Quantitative real time PCR was used for profiling the selected miRNA expression at various time intervals of the three defined groups of rats. In prediabetes and overt diabetes stages, miR-103 showed significantly elevated expression in PBMC specimens compared to the normal healthy control group. Overexpression pattern of mir-143 was statistically significant in T2D compared to non-diabetic controls. However in HFD (prediabetic) rats also we observed an increasing pattern of miR-143 compared to the normal controls but it was not statistically significant.

摘要

从正常糖耐量(NGT)进展到2型糖尿病(T2D)是通过一种称为糖尿病前期的糖耐量异常中间状态发生的。这种转变通常是一个渐进的现象,发生在5至10年的时间里。在常规使用的T2D筛查标准中,如空腹血糖(FPG)、空腹血糖受损(IFG)、糖耐量受损(IGT)或糖化血红蛋白(HbA1c),关于哪种更优的问题仍存在争议。新出现的微小RNA为成为一类在疾病发展早期可检测到的合适的糖尿病基因标志物带来了很大希望。尽管已报道了主要胰岛素靶器官中与T2D相关的微小RNA波动,但由于其侵入性,为了筛查而对这些器官进行采样是不可行的。外周血单个核细胞(PBMC)与所有身体器官持续接触,因此可能表现出胰岛素靶器官中发生的微小RNA变化的痕迹。在本研究中,我们评估了三组大鼠中miR - 103和miR - 143的表达,这三组分别是:正常对照组、对应糖尿病前期状态的高脂饮食(HFD)组以及高脂饮食/链脲佐菌素(STZ)诱导的T2D组。采用定量实时PCR对三组定义的大鼠在不同时间间隔的选定微小RNA表达进行分析。在糖尿病前期和显性糖尿病阶段,与正常健康对照组相比,PBMC标本中miR - 103的表达显著升高。与非糖尿病对照组相比,miR - 143在T2D中的过表达模式具有统计学意义。然而,在HFD(糖尿病前期)大鼠中,与正常对照组相比,我们也观察到miR - 143有增加的趋势,但无统计学意义。

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