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Resveratrol (RSV) and metformin (MET) play a role in the treatment of diabetes; however, the mechanisms through which they mediate insulin resistance by regulating long non‑coding RNAs (lncRNAs) remain unknown. The present study was conducted to determine whether RSV and MET can improve insulin resistance in the livers of high‑fat diet (HFD)‑fed mice by regulating lncRNAs. C57BL/6J mice were fed a HFD for 8 weeks to establish a model of insulin resistance. The mice were subsequently treated with RSV or MET for 8 weeks and liver tissue samples were then collected. High‑throughput sequencing was utilized to analyze mouse liver tissue samples to obtain differential lncRNA expression profiles. RSV or MET both reduced the blood glucose levels, the insulin index and the area under the curve in HFD‑fed mice. Treatment also improved liver structure and decreased lipid deposition in liver tissues, as shown by H&amp;E and Oil Red O staining. Compared with the MET group, there were 55 lncRNAs and 19 mRNAs with a differential expression. In total, eight lncRNAs were randomly selected and evaluated by reverse transcription‑quantitative PCR (RT‑qPCR). The results of seven lncRNAs corresponded to those of the sequencing analysis. Pathway analysis revealed that the PI3K/Akt signaling pathway had the highest enrichment score. In addition, the results of western blot analysis and RT‑qPCR revealed that the expression levels of forkhead box O1, glucose‑6‑phosphatase catalytic subunit 1 and phosphoenolpyruvate carboxykinase 1 in the RSV and MET groups were significantly decreased compared with those in the HFD group. NONMMUT034936.2 and G6PC target genes exhibited similar expression patterns, indicating that RSV and MET may affect the PI3K/Akt signaling pathway through NONMMUT034936.2 to attenuate insulin resistance. On the whole, the present study provides novel biomarkers or contemporary perspectives for the use of RSV and MET in the treatment of insulin resistance and diabetes.

Comparative analysis of long non‑coding RNA expression profiles induced by resveratrol and metformin treatment for hepatic insulin resistance