miR-450a-5p Eliminates MGO-Induced Insulin Resistance via Targeting CREB

BACKGROUND AND OBJECTIVES: miR-450a-5p was involved in fat formation, however, its role in insulin resistance remains unclear. This study investigated the effects of miR-450a-5p on endothelial cells, with the aim of finding a potential target for diabetes mellitus. METHODS AND RESULTS: Human umbilical vein endothelial cells (HUVECs) were treated with low-glucose, high-glucose, methylglyoxal (MGO), and insulin alone or in combination with MGO. The expression of miR-450a-5p in treated cells was measured by quantitative real-time polymerase chain reaction (qRT-PCR) assays. The cell activity, migration and fat formation were determined by MTT experiments, Transwell assay and oil red O staining. The expressions of eNOS/AKT pathway-related proteins in cells were assessed by Western blot (WB) analysis. Furthermore, the target gene of miR-450a-5p was analyzed by double-luciferase reporter analysis, and its effects on eNOS/AKT pathway were estimated. We found that the expression of miR-450a-5p was decreased obviously in endothelial cells treated with high-glucose and MGO. In vitro cell experiments showed that MGO could not only promote the activity of endothelial cells, but also accelerate cell migration and fat accumulation, which, however, could be reversed by up-regulation of miR-450a-5p. Moreover, MGO inhibited eNOS/AKT pathway activation and NO release mediated by insulin, and such effects were reversed by up-regulation of miR-450a-5p. Furthermore, CREB was the target gene for miR-450a-5p, had an activation effect on the eNOS/AKT pathway. CONCLUSIONS: Up-regulated miR-450a-5p eliminates MGO-induced insulin resistance via targeting CREB, and therefore could be used as a potential target to improve insulin resistance and treat patients with diabetes-related diseases.