Dahlmans Dennis, Houzelle Alexandre, Jörgensen Johanna A, Phielix Esther, Lindeboom Lucas, Hesselink Matthijs K C, Schrauwen Patrick, Hoeks Joris
Departments of Human Biology and Human Movement Sciences, Maastricht University Medical CenterMaastricht, Netherlands.
Departments of Radiology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical CenterMaastricht, Netherlands.
Front Physiol. 2017 Sep 21;8:711. doi: 10.3389/fphys.2017.00711. eCollection 2017.
In recent years, several microRNAs (miRNAs)-post-transcriptional regulators of gene expression-have been linked to the regulation of peripheral insulin sensitivity. Many of these studies, however, have been conducted in cell or animal models and the few human studies available lack adequate measurements of peripheral insulin sensitivity. In the present study, we examined the expression of 25 miRNAs, putatively involved in (peripheral) insulin sensitivity, in skeletal muscle biopsies from extensively phenotyped human individuals, widely ranging in insulin sensitivity. To identify miRNAs expressed in skeletal muscle and associated with insulin sensitivity and type 2 diabetes, a comprehensive PubMed-based literature search was performed. Subsequently, the expression of selected miRNAs was determined by RT-qPCR using predesigned 384-well Pick-&-Mix miRNA PCR Panel plates in muscle biopsies from type 2 diabetes patients, non-diabetic obese/overweight individuals, lean sedentary individuals and endurance-trained athletes. In all subjects, peripheral insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. The literature search resulted in 25 candidate miRNAs, 6 of which were differentially expressed in human type 2 diabetes compared to non-diabetic obese/overweight individuals. In turn, four of these miRNAs, i.e., miRNA27a-3p ( = -0.45, = 0.0012), miRNA-29a-3p ( = -0.40, = 0.0052), miRNA-29b-3p ( = -0.70, < 0.0001) and miRNA-29c-3p ( = -0.50, = 0.0004) demonstrated strong negative correlations with peripheral insulin sensitivity across all four subject groups. We identified miR-27a-3p and all members of the miRNA-29 family as potential regulatory players in insulin sensitivity in humans. These miRNA's may represent interesting novel targets for maintaining or improving insulin sensitivity.
近年来，几种微小RNA（miRNA）——基因表达的转录后调节因子——已被证明与外周胰岛素敏感性的调节有关。然而，这些研究大多是在细胞或动物模型中进行的，现有的少数人体研究缺乏对外周胰岛素敏感性的充分测量。在本研究中，我们检测了25种可能参与（外周）胰岛素敏感性调节的miRNA在胰岛素敏感性差异很大的大量表型化个体的骨骼肌活检组织中的表达情况。为了鉴定在骨骼肌中表达且与胰岛素敏感性和2型糖尿病相关的miRNA，我们进行了基于PubMed的全面文献检索。随后，使用预先设计的384孔Pick-&-Mix miRNA PCR板通过RT-qPCR测定2型糖尿病患者、非糖尿病肥胖/超重个体、久坐不动的瘦人以及耐力训练运动员的肌肉活检组织中所选miRNA的表达。在所有受试者中，通过高胰岛素-正葡萄糖钳夹技术测量外周胰岛素敏感性。文献检索得到25种候选miRNA，其中6种在2型糖尿病患者与非糖尿病肥胖/超重个体中差异表达。反过来，这6种miRNA中的4种，即miRNA27a-3p（r = -0.45，P = 0.0012）、miRNA-29a-3p（r = -0.40，P = 0.0052）、miRNA-29b-3p（r = -0.70，P < 0.0001）和miRNA-29c-3p（r = -0.50，P = 0.0004）在所有四个受试者组中均与外周胰岛素敏感性呈强烈负相关。我们确定miR-27a-3p和miRNA-29家族的所有成员是人类胰岛素敏感性的潜在调节因子。这些miRNA可能是维持或改善胰岛素敏感性的有趣新靶点。
