Demirsoy İbrahim Halil, Ertural Duygu Yolal, Balci Şenay, Çınkır Ümit, Sezer Kerem, Tamer Lülüfer, Aras Nurcan
Department of Medical Biology, Mersin University, Mersin, Turkey.
Department of Medical Biochemistry, Mersin University, Mersin, Turkey.
J Med Biochem. 2018 Dec 1;37(4):499-506. doi: 10.2478/jomb-2018-0009. eCollection 2018 Dec.
Metformin, a widely used biguanide class of anti-diabetic drug, has potential to increase insulin sensitivity and reduce blood glucose to treat type 2 diabetes (T2D). It has been reported that metformin has an activity on regulation of miRNAs by targeting several downstream genes in metabolic pathways. However, molecular mechanism underlying the process is still not fully known. In this study, it was aimed to identify differential expression profiles of plasma derived miRNAs following 3 months metformin treatment in patients with T2D.
The plasma samples of 47 patients with T2D (received no anti-diabetic treatments) and plasma samples of same 47 patients received 3 months metformin treatment was recruited to the study. Total RNAs were isolated from plasma and reverse transcribed into cDNA. Profiles of differential expressions of miRNAs in plasma were assessed by using of micro-fluidic based multiplex quantitative real time -PCR (BioMarkTM 96.96 Dynamic Array).
Our results showed that expression profiles of 13 candidate miRNAs; hsa-let-7e-5p, hsa-let-7f-5p, hsa-miR- 21-5p, hsa-miR-24-3p, hsa-miR-26b-5p, hsa-miR-126-5p, hsa-miR-129-5p, hsa-miR-130b-3p, hsa-miR-146a-5p, hsamiR- 148a-3p, hsa-miR-152-3p, hsa-miR-194-5p, hsa-miR- 99a-5p were found significantly downregulated following metformin treatments in patients with T2D (p<0.05).
In conclusion, our finding could provide development of better and more effective miRNAs based therapeutic strategies against T2D.
二甲双胍是一种广泛使用的双胍类抗糖尿病药物,具有增加胰岛素敏感性和降低血糖以治疗2型糖尿病(T2D)的潜力。据报道,二甲双胍通过靶向代谢途径中的几个下游基因对miRNA的调节具有活性。然而,该过程的分子机制仍不完全清楚。在本研究中,旨在确定T2D患者接受3个月二甲双胍治疗后血浆来源miRNA的差异表达谱。
招募47例未接受抗糖尿病治疗的T2D患者的血浆样本以及同一47例接受3个月二甲双胍治疗的患者的血浆样本进行研究。从血浆中分离总RNA并逆转录为cDNA。通过基于微流控的多重定量实时PCR(BioMarkTM 96.96动态阵列)评估血浆中miRNA的差异表达谱。
我们的结果显示,13种候选miRNA的表达谱;hsa-let-7e-5p、hsa-let-7f-5p、hsa-miR-21-5p、hsa-miR-24-3p、hsa-miR-26b-5p、hsa-miR-126-5p、hsa-miR-129-5p、hsa-miR-130b-3p、hsa-miR-146a-5p、hsa-miR-148a-3p、hsa-miR-152-3p、hsa-miR-194-5p、hsa-miR-99a-5p在T2D患者接受二甲双胍治疗后显著下调(p<0.05)。
总之,我们的发现可为开发更好、更有效的基于miRNA的T2D治疗策略提供依据。