Circulating miR-192 and miR-193b Are Markers of Prediabetes and Are Modulated by an Exercise Intervention
Circulating miR-192 and miR-193b Are Markers of Prediabetes and Are Modulated by an Exercise Intervention
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DOI：
10.1210/jc.2014-2574
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发表时间：
2015-03-01
影响因子：
5.8
通讯作者：
Novials, Anna
中科院分区：
文献类型：
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作者：
Parrizas, Marcelina;Brugnara, Laura;Novials, Anna
背景：糖尿病往往诊断较晚，此时并发症的发生几乎不可避免，降低了患者的生活质量。然而，早期发现受影响的个体将允许实施及时和有效的治疗。目的：本文旨在描述糖尿病前期患者循环microRNAs （miRNAs）的特征，以确定新的诊断和治疗工具。设计：我们使用实时RT-PCR技术测量了92名空腹血糖或糖耐量受损的对照组和糖尿病前期患者以及新诊断的糖尿病患者血清中176种mirna的丰度。我们在第二组接受治疗性运动干预的对照组和糖尿病前期受试者以及葡萄糖耐受不良小鼠模型中验证了这一结果。结果：我们发现了两个mirna， miR-192和miR-193b，它们的丰度在糖尿病前期显著增加，而在糖尿病患者中没有。引人注目的是，这些mirna在葡萄糖不耐受小鼠的血浆中也有所增加。此外，在糖尿病前期人和葡萄糖不耐受小鼠中，经过包括慢性运动在内的治疗性干预，miR-192和miR-193b的循环水平都恢复到基线水平，从而成功地使代谢参数正常化。结论：我们的数据表明，在小鼠和人类中，循环mirna的模式以类似的方式被葡萄糖代谢缺陷所修饰。这种循环miRNA标记可以作为一种新的诊断工具，以及监测对干预的反应。
Context: Diabetes is frequently diagnosed late, when the development of complications is almost inevitable, decreasing the quality of life of patients. However, early detection of affected individuals would allow the implementation of timely and effective therapies.Objective: Here we set to describe the profile of circulating microRNAs (miRNAs) in prediabetic patients with the intention of identifying novel diagnostic and therapeutic tools.Design: We used real-time RT-PCR to measure the abundance of 176 miRNAs in serum of a cohort of 92 control and prediabetic individuals with either impaired fasting glucose or impaired glucose tolerance, as well as newly diagnosed diabetic patients. We validated the results in a second cohort of control and prediabetic subjects undergoing a therapeutic exercise intervention, as well as in a mouse model of glucose intolerance.Results: We identified two miRNAs, miR-192 and miR-193b, whose abundance is significantly increased in the prediabetic state but not in diabetic patients. Strikingly, these miRNAs are also increased in plasma of glucose-intolerant mice. Moreover, circulating levels of miR-192 and miR-193b return to baseline in both prediabetic humans and glucose-intolerant mice undergoing a therapeutic intervention consisting in chronic exercise, which succeeded in normalizing metabolic parameters.Conclusions: Our data show that the pattern of circulating miRNAs is modified by defects in glucose metabolism in a similar manner in mice and humans. This circulating miRNA signature for prediabetes could be used as a new diagnostic tool, as well as to monitor response to intervention.