Resistin is expressed in human hepatocytes and induces insulin resistance
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Resistin, known as an adipocyte-specific secretory factor (ADSF), is implicated to modulate insulin resistance in rodents. However, the precise role of this factor for human insulin resistance has remained elusive. Here, we investigate the relationship between human resistin and insulin resistance in hepatocytes and the effect of Metformin on resistin. In this study, the expression of resistin in human hepatocytes and hepatic tissues was examined, and the human resistin eukaryotic expression vector was constructed and stably transfected in HepG2 cells. Data showed that resistin is expressed in human hepatocytes and hepatic tissues. Overexpression of human resistin impaired significantly insulin-stimulated glucose uptake and glycogen synthesis in HepG2 cells. It also decreased the expression of insulin receptor substrate 2 (IRS-2) and c-cbl associated protein (CAP), whereas increased the expression of glycogen synthetase kinase 3β (GSK-3β). The result suggested that human resistin induced insulin resistance in hepatocytes by blocking the two insulin signal transduction pathways of PI-3K/Akt and of CAP/c-cbl. We also concluded that Metformin reversed the effect of resistin and downregulated the expression of resistin in hepatocytes.
KeywordsHuman resistin HepG2 cells Insulin resistance Insulin signal transduction pathway Metformin
Thanks to Professor PEI YIN ZHANG (Jilin University) for his great help in assays of glucose uptake. This work was supported by the National Natural Science Foundation of China (No. 39870667) and program for Scientific Research Foundation of Jilin Province (No.20020704).
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