Characterization of Micro-RNA Changes during the Progression of Type 2 Diabetes in Zucker Diabetic Fatty Rats.
Characterization of Micro-RNA Changes during the Progression of Type 2 Diabetes in Zucker Diabetic Fatty Rats.
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DOI：
10.3390/ijms17050665
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发表时间：
2016-05-03
影响因子：
5.6
通讯作者：
Grempler R
中科院分区：
文献类型：
--
作者：
Delic D;Eisele C;Schmid R;Luippold G;Mayoux E;Grempler R
本初步研究的目的是鉴定Zucker糖尿病脂肪大鼠（ZDF大鼠）在2型糖尿病（T2D）发生和进展过程中微rna随时间的变化。T2D是一种复杂的代谢紊乱，其特点是胰腺β细胞产生胰岛素的进行性衰竭，而且其他器官（如肝脏、脂肪组织和心血管系统）的功能或形态改变。微rna是一类新的生物标志物，有潜力代表疾病进展的生物标志物。在这项研究中，从6周龄到17周龄的ZDF大鼠追踪糖尿病的发生和进展。在高胰岛素血症的初始阶段之后，这些动物发展为T2D，失去了产生足够胰岛素的能力。使用TaqMan miRNA阵列从四个时间点的血浆样本中测量循环miRNA：糖尿病前期（6周龄）、高胰岛素血症（8周）、β细胞衰竭（11周）和晚期糖尿病（17周）。生物信息学分析揭示了循环mirna随时间的明显变化。研究发现，在疾病进展过程中，miR-122、miR-133、miR-210和miR-375等几种mirna水平升高。下降最显著的mirna是miR-140、miR-151-3p、miR-185、miR-203、miR-434-3p和miR-450a。最近在2型糖尿病患者中也发现了一些mirna，因此可能有潜力成为T2D疾病进展和/或抗糖尿病药物治疗反应的有用生物标志物。
The aim of the present pilot study was the identification of micro-RNA changes over time during the development and progression of type 2 diabetes (T2D) in Zucker diabetic fatty rats (ZDF rats). T2D is a complex metabolic disorder that is characterized, inter alia, by progressive failure of pancreatic β cells to produce insulin, but also by functional or morphological modifications of others organ, such as liver, adipose tissue and the cardiovascular system. Micro-RNAs are a novel class of biomarkers that have the potential to represent biomarkers of disease progression. In this study, the onset and progression of diabetes was followed in ZDF rats from six weeks until 17 weeks of age. After an initial phase of hyperinsulinemia, the animals developed T2D and lost the capacity to produce sufficient insulin. Circulating miRNAs were measured from plasma samples at four time points: pre-diabetes (six weeks of age), hyperinsulinemia (eight weeks), β cell failure (11 weeks) and late-stage diabetes (17 weeks) using TaqMan miRNA arrays. Bioinformatic analysis revealed distinct changes of circulating miRNAs over time. Several miRNAs were found to be increased over the course of the disease progression, such as miR-122, miR-133, miR-210 and miR-375. The most significantly decreased miRNAs were miR-140, miR-151-3p, miR-185, miR-203, miR-434-3p and miR-450a. Some of the miRNAs have also been identified in type 2 diabetic patients recently and, therefore, may have the potential to be useful biomarkers for the disease progression of T2D and/or the treatment response for anti-diabetic medications.