SummaryBackgroundMetformin, 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.MethodsThe 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).ResultsOur 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).ConclusionsIn conclusion, our finding could provide development of better and more effective miRNAs based therapeutic strategies against T2D.

Although smoking is regarded as the most important causal factor in chronic obstructive pulmonary disease (COPD), only 10-20% of smokers develop symptomatic COPD, which indicates the presence of genetic predisposing factors in its pathogenesis. This study investigates the association between gene polymorphysims of glutathione S-transferases (GSTs) and COPD. Blood samples were taken from 149 patients and 150 healthy controls. Polymorphisms of GSTT1, GSTM1, and GSTP1 were genotyped using Real-Time PCR. Multivariate logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals between specific genotypes and COPD. There was no difference in the frequencies of the genotypes of GSTM1 and GSTT1 between the groups, but the GSTP1 Ile/Ile genotype was significantly higher in the patients than in the controls (61.1% vs. 38%). GSTP1 Ile/Val and Val/Val genotypes were associated with a decreased risk of COPD when compared to the Ile/Ile genotype (2.12-fold and 4-fold, respectively). Thus we suggest that the Val allele of GSTP1 may have a protective effect for development of COPD. Furthermore, when we evaluated the association between GSTP1 genes and smoking status, smokers with the GSTP1 Ile allele had an increased risk for the development of COPD. Among the combinations of the genotypes, the combination of GSTM1, GSTT1 null, and GSTP1 Val/Val was associated with the maximal increased risk (12-fold) of COPD. Thus to explain the ethiopathogenesis of COPD, investigation of a single gene family is inadequate. Based on our results and the previous data, further studies should be focused on the GSTP1 gene and the interactions with other genes such as polymorphisms of N-acetyltransferases, GSTM1 and GSTT1, microsomal epoxide hydrolase, and allelic variants of cytochrome P450.