Regulation of insulin resistance by targeting the insulin-like growth factor 1 receptor with microRNA-122-5p in hepatic cells.

Insulin resistance (IR) is a common etiology of type 2 diabetes (T2D) defined by a state of decreased reactivity to insulin in multiple organs, such as the liver. This study aims to investigate how microRNA-122-5p (miR-122) regulates the hepatic IR in vitro. We first found that the miR-122 level was upregulated in the liver of rats fed with a high-fat diet and injected with streptozotocin (T2D rats), while the expression level of insulin-like growth factor 1 receptor (IGF-1R), a potential target of miR-122, was downregulated in the diabetic liver. In vitro, glucosamine-induced IR was introduced in HepG2 hepatic cells, and the levels of miR-122 and IGF-1R were further assessed. An increase of miR-122 level and a decrease of IGF-IR level were observed in IR hepatic cells, which was the same as that in the diabetic liver. Results of the luciferase reporter assay validated IGF-1R as a direct target of miR-122. Moreover, in IR HepG2 cells, antagonizing miR-122 with its specific inhibitor enhanced glucose uptake and suppressed the expression of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase, two key enzymes in regulating gluconeogenesis. Such alterations induced by the miR-122 inhibitor in IR hepatic cells were impaired when IGF-1R was simultaneously knocked down. In addition, the PI3K/Akt pathway was deactivated in IR cells, and then reactivated with miR-122 inhibitor transfection. In conclusion, our study demonstrates that miR-122 is able to regulate IR in hepatic cells by targeting IGF-1R.

Cytoprotection of perfluorocarbon on PMVECs in vitro.

Lipopolysaccharide (LPS) can activate endothelial cells and induce inflammatory injury. Toll-like receptor-4 (TLR-4) is integrally involved in LPS signaling and has a requisite role in the activation of nuclear factor (NF)-κB. A number of studies have demonstrated the cytoprotective action of perfluorocarbon (PFC) both in vivo and in vitro, but the exact mechanisms have yet to be elucidated. In this study, we examined in an in vitro model the cytoprotective effect of PFC on LPS-stimulated pulmonary vascular endothelial cells (PMVECs). Intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), and interleukin-8 (IL-8) were significantly increased in the LPS-stimulated PMVECs groups. The expression of TLR-4 mRNA and protein in LPS groups was markedly increased. Meanwhile, NF-κB was activated. There were no significant effects of PFC alone on any of the factors studied while the coculture group showed significant downregulation of the secretion of ICAM-1, TNF-α, and IL-8; the expression of TLR-4 mRNA; and the activity of NF-κB. LPS can induce PMVEC inflammatory injury via the activation of TLR-4 and subsequent activation of NF-κB. PFC is able to protect PMVECs from LPS-induced inflammatory injury by blocking the initiation of the LPS signaling pathway.