Abstract
Resveratrol (RSV) and long non‑coding RNAs (lncRNAs) play a role in the treatment of diabetes; however, the mechanism by which resveratrol regulates insulin resistance via lncRNAs is currently unknown. The present study aimed to determine the lncRNA expression level profile in mice following resveratrol treatment to improve insulin resistance using high‑throughput sequencing technology. C57BL/6J mice were fed a high‑fat diet for 8 weeks to develop an insulin resistance model, followed by treatment with or without RSV for 6 weeks before high‑throughput sequencing. Following RSV treatment, 28 and 30 lncRNAs were up‑ and downregulated, respectively; eight lncRNAs were randomly selected and evaluated using reverse transcription‑quantitative PCR, which showed results consistent with the sequencing analysis. Pathway analysis demonstrated that the insulin signaling pathway enrichment score was the highest, and identified two lncRNAs, NONMMUT058999.2 and NONMMUT051901.2, consistent with the protein‑encoding genes SOCS3 and G6PC, respectively. Similar expression level patterns were observed for SOCS3 and G6PC, suggesting that RSV improves insulin resistance by modulating lncRNAs. RSV decreased the expression levels of SOCS3, FOXO1, G6PC and PEPCK in mice. The same results were observed following knockdown of NONMMUT058999.2 in cells. The present study provides a new biomarker or intervention target for RSV in the treatment of diabetes, and a new perspective for understanding the hypoglycemic mechanism of RSV.