Insulin resistance (IR) is a complex pathological condition resulting from the dysregulation of cellular response to insulin hormone in insulin-dependent cells and is recognized as a pathogenic hallmark and strong risk factor for metabolic syndrome. The present study aims to elucidate the molecular mechanism of the pathogenesis of IR. Here, we used human umbilical vein endothelial cells (HUVECs) to establish the IR cell model induced by 1 × 10-6 mmol/L insulin. After 48 h, reactive oxygen species (ROS) and glucose consumption were measured by DCFH-DA and GOD-POD methods, respectively. The results of Microarray analysis demonstrated that there were 10 differentially expressed miRNAs (DEMs) selected based on Fold change (FC) and P value in the IR cell model compared with HUVECs. The enriched gene ontology (GO) terms analysis showed that the target genes of these 10 DEMs were significantly enriched in biological process, cellular component and molecular function, and the significantly enriched Kyoto Encyclopedia of Genes or Genomes (KEGG) pathways mainly include AMPK signaling pathway and PI3K signaling pathway. Amongst all, the expression level of miR-3138 was highest in the IR cell model evaluated by qRT-PCR. Through Targetscan, KSR2 mRNA was predicted as a target of miR-3138. And mRNA and protein expression levels of miR-3138, KSR2, GLUT4, AMPK, PI3K, Akt were examined using qRT-PCR and Western blotting, respectively. The interaction between miR-3138 and KSR2 was evaluated by dual-luciferase reporter assay. Our results showed that miR-3138 significantly deteriorated the IR of HUVECs via KSR2/AMPK/GLUT4 signaling pathway.
Keywords: AMPK; GLUT4; KSR2; MiR-3138; insulin resistance.