miRNA-375 a Sensor of Glucotoxicity Is Altered in the Serum of Children with Newly Diagnosed Type 1 Diabetes.
miRNA-375 a Sensor of Glucotoxicity Is Altered in the Serum of Children with Newly Diagnosed Type 1 Diabetes.
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miRNA-375在新诊断的1型糖尿病的儿童的血清中，糖毒性的传感器改变了。
DOI：
10.1155/2016/1869082
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发表时间：
2016
影响因子：
4.3
通讯作者：
Rome S
中科院分区：
文献类型：
--
作者：
Marchand L;Jalabert A;Meugnier E;Van den Hende K;Fabien N;Nicolino M;Madec AM;Thivolet C;Rome S
背景资料。使用miRNAs作为1型糖尿病(T1D)风险的生物标志物是有吸引力的，因为T1D通常在急性症状之前被诊断出来。由于miR-375在内分泌胰腺中高表达，我们推测其循环水平可能反映了β细胞的变化，并可能在新近诊断的T1D患者的血液中发生变化。方法：研究方法。22名T1D儿童在发病时、皮下胰岛素治疗前和10名非糖尿病儿童对照中采集血清。采用基于茎环RT-PCR的方法检测MIR-375血清水平。用TaqMan低密度阵列检测高糖环境下人胰岛中miRNAs的表达。结果。在人类胰岛中检测到的410个miRNAs中，miR-375的丰度反映了它在啮齿动物胰岛生物学中的既定作用。上调的miRNAs靶向基因涉及胰岛的动态平衡和β细胞质量的调节。下调的miRNAs，包括miR-375，与胰腺分泌和蛋白质周转有关。与年龄匹配的对照组相比，T1D儿童血清miR-375水平较低，与糖化血红蛋白、血糖和自身抗体的数量没有任何相关性。结论。在T1D开始时，循环miR-375水平的改变可能是与疾病相关的代谢改变和炎症的一般生物标志物。
Background. The use of miRNAs as biomarkers for Type 1 Diabetes (T1D) risk is attractive as T1D is usually diagnosed in front of acute symptoms. As miR-375 is highly expressed in the endocrine pancreas, we postulated that its circulating level might reflect beta cell alterations and might be altered in the blood of T1D patients recently diagnosed. Methods. Sera were obtained from 22 T1D children at onset of the disease, before subcutaneous insulin treatment, and from 10 nondiabetic pediatric controls. MiR-375 seric level was quantified by stem-loop RT-PCR-based assay. MiRNAs regulations in isolated human islets in response to high glucose concentrations were determined by TaqMan Low-Density Array. Results. The abundance of miR-375, among the 410 miRNAs detected in human islets, mirrored its well-established role in rodent islet biology. Upregulated miRNAs targeted genes involved in islet homeostasis and regulation of beta cell mass. Downregulated miRNAs, including miR-375, were involved in pancreas secretion and protein turnover. Seric level of miR-375 was lower in T1D children versus age-matched controls, without any correlations with HbA1c, glycaemia, and number of autoantibodies. Conclusion. Altered circulating level of miR-375 at onset of T1D might be a general biomarker of metabolic alterations and inflammation associated with the disease.