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口服葡萄糖耐量试验揭示了肥胖学龄前儿童中与胰岛素抵抗相关的循环微小RNA。

Oral glucose tolerance test unravels circulating miRNAs associated with insulin resistance in obese preschoolers.

作者信息

Masotti A, Baldassarre A, Fabrizi M, Olivero G, Loreti M C, Giammaria P, Veronelli P, Graziani M P, Manco M

机构信息

Gene expression - Microarrays Laboratory, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Research Unit for Multifactorial Disease, Scientific Directorate, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

出版信息

Pediatr Obes. 2017 Jun;12(3):229-238. doi: 10.1111/ijpo.12133. Epub 2016 Apr 5.

Abstract

BACKGROUND

Circulating microRNAs (miRNAs) may act as biomarkers of metabolic disturbances.

OBJECTIVE

The aim of this study was to identify serum miRNAs signature of early insulin resistance in obese preschoolers.

METHODS

Twelve obese children, aged 2-6 years, six insulin resistant (IR) and six controls were selected being age-matched, sex-matched and body mass index-matched. Profiling of 179 circulating miRNAs, known to be widely expressed in the bloodstream, was investigated by quantitative polymerase chain reaction at fasting and 120 min following a standard oral glucose tolerance test (OGTT).

RESULTS

Twenty-one miRNAs were differentially regulated in IR obese preschoolers. miR-200c-3p, miR-190a and miR-95 were differently regulated both at fasting and 120 min after the OGTT. In controls, the fold changes of some miRNAs were correlated with Δglucose (miR-660, miR-26b-5p and miR-22-3p: p = 0.005 for all) and Δinsulin (miR-660 and miR-22-3p: p = 0.02 for both and miR-423-5p: p = 0.042). In IR patients, miR-1 fold changes were correlated with Δglucose r = -0.786; p = 0.036) and Δinsulin r = -0.821; p = 0.023).

CONCLUSIONS

Our study identifies circulating miR-200c-3p, miR-190a and miR-95 as biomarkers of insulin resistance in obese preschoolers, being differentially regulated in IR patients both in fasting condition and after the OGTT. Expression of some circulating miRNAs seems reflecting glucose and insulin excursion following the OGTT differently in controls and IR obese preschoolers.

摘要

背景

循环微RNA(miRNA)可能作为代谢紊乱的生物标志物。

目的

本研究旨在确定肥胖学龄前儿童早期胰岛素抵抗的血清miRNA特征。

方法

选取12名2至6岁的肥胖儿童,其中6名胰岛素抵抗(IR)儿童和6名对照儿童,年龄、性别和体重指数相匹配。通过定量聚合酶链反应,对已知在血液中广泛表达的179种循环miRNA进行分析,检测空腹时以及标准口服葡萄糖耐量试验(OGTT)后120分钟时的情况。

结果

21种miRNA在IR肥胖学龄前儿童中存在差异调节。miR-200c-3p、miR-190a和miR-95在空腹时以及OGTT后120分钟时均有不同调节。在对照组中,一些miRNA的倍数变化与Δ葡萄糖(miR-660、miR-26b-5p和miR-22-3p:均p = 0.005)和Δ胰岛素(miR-660和miR-22-3p:均p = 0.02,miR-423-5p:p = 0.042)相关。在IR患者中,miR-1的倍数变化与Δ葡萄糖(r = -0.786;p = 0.036)和Δ胰岛素(r = -0.821;p = 0.023)相关。

结论

我们的研究确定循环miR-200c-3p、miR-190a和miR-95为肥胖学龄前儿童胰岛素抵抗的生物标志物,在IR患者的空腹状态和OGTT后均有差异调节。一些循环miRNA的表达似乎在对照组和IR肥胖学龄前儿童中对OGTT后的葡萄糖和胰岛素波动反映不同。

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