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Diabetes Care:研究评估循环miRNA与2型糖尿病的相关性

来源:生物谷 2014-02-08 21:23

2014年2月8日讯 /生物谷BIOON/--根据Diabetes Care杂志上公布的一项研究报告证实:体内循环微小RNA(miRNA)的某些特性与2型糖尿病(T2D)存在相关性,其水平随胰岛素的作用而改变。

Francisco J. Ortega博士和同事评估了12位男性中循环miRNA的特征:6位糖耐量正常(NGT)者和六位T2D。

在45位NGT和48位T2D的更大样本中,验证了10个循环miRNA与T2D的关联性。在这样研究中,35例T2D被招募进行了纵向评估,7名健康志愿者中,循环miRNA在高胰岛素钳夹法和胰岛素加脂肪乳剂/肝素注射六小时之前和之后被评估。

对于T2D患者,研究人员发现三个miRNA增加与七个miRNA减少。在控制了混杂因素后,miR-140-5p和miR-423-5p占空腹血糖变异的49.5%。四个miRNA(miR-140-5p,miR-423-5p,miR-195和miR-126)与T2D具有相关性,精确度为89.2%。

循环miR-192,miR-140-5p,和miR-22在二甲双胍治疗组,但未在安慰剂组中观察到显著变化,并且与空腹血糖和糖基化血红蛋白降低成平行关系。

胰岛素输注组参试者中miR-22降低,同时脂肪乳剂/肝素混合物组中,循环miR-222和miR-140-5p增加。这项研究主要描述了循环miRNAs变化与T2D的相关性。(生物谷Bioon.com)

 

Profiling of Circulating MicroRNAs Reveals Common MicroRNAs Linked to Type 2 Diabetes That Change With Insulin Sensitization

Francisco J. Ortega, et al.

OBJECTIVE This study sought to identify the profile of circulating microRNAs (miRNAs) in type 2 diabetes (T2D) and its response to changes in insulin sensitivity.

RESEARCH DESIGN AND METHODS The circulating miRNA profile was assessed in a pilot study of 12 men: 6 with normal glucose tolerance (NGT) and 6 T2D patients. The association of 10 circulating miRNAs with T2D was cross-sectionally validated in an extended sample of 45 NGT vs. 48 T2D subjects (65 nonobese and 28 obese men) and longitudinally in 35 T2D patients who were recruited in a randomized, double-blinded, and placebo-controlled 3-month trial of metformin treatment. Circulating miRNAs were also measured in seven healthy volunteers before and after a 6-h hyperinsulinemic-euglycemic clamp and insulin plus intralipid/heparin infusion.

RESULTS Cross-sectional studies disclosed a marked increase of miR-140-5p, miR-142-3p, and miR-222 and decreased miR-423-5p, miR-125b, miR-192, miR-195, miR-130b, miR-532-5p, and miR-126 in T2D patients. Multiple linear regression analyses revealed that miR-140-5p and miR-423-5p contributed independently to explain 49.5% (P < 0.0001) of fasting glucose variance after controlling for confounders. A discriminant function of four miRNAs (miR-140-5p, miR-423-5p, miR-195, and miR-126) was specific for T2D with an accuracy of 89.2% (P < 0.0001). Metformin (but not placebo) led to significant changes in circulating miR-192 (49.5%; P = 0.022), miR-140-5p (?15.8%; P = 0.004), and miR-222 (47.2%; P = 0.03), in parallel to decreased fasting glucose and HbA1c. Furthermore, while insulin infusion during clamp decreased miR-222 (?62%; P = 0.002), the intralipid/heparin mixture increased circulating miR-222 (163%; P = 0.015) and miR-140-5p (67.5%; P = 0.05).

CONCLUSIONS This study depicts the close association between variations in circulating miRNAs and T2D and their potential relevance in insulin sensitivity.

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