Sheng Chun Hua, Di Jun, Jin Yong, Zhang Yu Cheng, Wu Mei, Sun Ying, Zhang Gui Zhen
Department of Central Research, The Third Clinical College, Jilin University, Xiantai Street No. 126, Changchun, 130033, China.
Endocrine. 2008 Apr;33(2):135-43. doi: 10.1007/s12020-008-9065-y. Epub 2008 Apr 30.
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 3beta (GSK-3beta). 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.
抵抗素，作为一种脂肪细胞特异性分泌因子（ADSF），被认为可调节啮齿动物的胰岛素抵抗。然而，该因子对人类胰岛素抵抗的确切作用仍不清楚。在此，我们研究人类抵抗素与肝细胞胰岛素抵抗之间的关系以及二甲双胍对抵抗素的影响。在本研究中，检测了人类肝细胞和肝组织中抵抗素的表达，并构建了人类抵抗素真核表达载体，将其稳定转染至HepG2细胞中。数据显示抵抗素在人类肝细胞和肝组织中表达。人类抵抗素的过表达显著损害了HepG2细胞中胰岛素刺激的葡萄糖摄取和糖原合成。它还降低了胰岛素受体底物2（IRS-2）和c-cbl相关蛋白（CAP）的表达，而增加了糖原合成酶激酶3β（GSK-3β）的表达。结果表明，人类抵抗素通过阻断PI-3K/Akt和CAP/c-cbl这两条胰岛素信号转导途径诱导肝细胞胰岛素抵抗。我们还得出结论，二甲双胍可逆转抵抗素的作用并下调肝细胞中抵抗素的表达。
