Background: 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.
Methods: 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).
Results: 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).
Conclusions: In conclusion, our finding could provide development of better and more effective miRNAs based therapeutic strategies against T2D.
Uvod: Metformin je široko upotrebljavan anti-dijabetični lek iz klase bigvanidina, koji potencijalno povećava insulinsku senzitivnost i umanjuje nivo glukoze u krvi pri tretmanu dijabetesa tip 2 (T2D). Ima podataka da metformin deluje i na regulisanje miRNA preko nekoliko niskosilaznih gena u metaboličkim putevima. Međutim, molekularni mehanizmi u ovom procesu nisu još uvek u potpunosti poznati. U ovom izučavanju svrha je bila da se identifikuju različiti ekspresioni profili miRNK u plazmi nakon tretmana T2D pacijenata sa metforminom.
Metode: Analizirani su uzorci plazme 47 pacijenata sa T2D (koji nisu bili na anti-dijabetičnom tretmanu) i uzorci plazme 47 pacijenata koji su 3 meseca primali metformin. Ukupna RNA je izolovana iz plazme i reverzno transkribovana u cDNK. Profili različitih ekspresija miRNK analizirani su primenom mikro-fluidne multipleks kvantitativne real-time PCR (BioMarkTM 96.96 Dynamyc Array).
Rezultati: Dobijeni rezultati pokazuju da je nađena ekspresija 13 kandidata miRNK; hsa-let-b-5p, hsa-let-7f-5p, hsamiR21-5p, hsa-miR-24-3p, hsa-miR-26-5p, hsa-miR-126-5p, hsa-miR-129, hsa-miR-130-3p, hsa-miR-146-5p, hsa-miR-148a-3p, hsa-miR-152-3p, hsa-miR-194-5p, hsa-miR-99a-5p, značajno snižena nakon tretmana metforminom pacijenata sa T2D (p<0,05).
Zaključak: Može se zaključiti da naši rezultati mogu unaprediti terapeutsku strategiju T2D zasnovanu na efektima miRNK.
Keywords: T2D; metformin; miRNAs; qRT-PCR.