Effect of metformin on the long non-coding RNA expression levels in type 2 diabetes: an in vitro and clinical trial study

Background It has been suggested that the anti-hyperglycemic effect of metformin could be associated with its impact on long non-coding RNA (lncRNA) expression levels. Accordingly, in the current study, we evaluated the effect of metformin on the expression of H19, MEG3, MALAT1, and GAS5 in in vitro and in vivo situations. Methods The effect of hyperglycemia and metformin treatment on the lncRNAs expression level was evaluated in HepG2 cells. A total of 179 age- and sex-matched subjects, including 88 newly diagnosed patients with type 2 diabetes (T2D) and 91 healthy volunteers, were included in the case-control phase of the study. Moreover, 40 newly diagnosed patients participated in the study's open-labeled non-controlled clinical trial phase. The expression levels of lncRNA in HepG2 cells and whole blood samples were determined using QRT-PCR. Results In vitro results showed that hyperglycemia induced H19 and MALAT1 and decreased GAS5 expression levels. Moreover, metformin decreased H19 and increased GAS5 expression in high glucose-treated cells. Case-control study findings revealed that the circulating levels of H19, MALAT1, and MEG3 were significantly elevated in T2D patients compared to the control subjects. Finally, results showed that the level of circulating H19 levels decreased while GAS5 increased in T2D patients after taking metformin for 2 months. Conclusion The results of the current study provided evidence that metformin could exert its effect in the treatment of T2D by altering the expression levels of H19 and GAS5.