title: Genistein reverses free fatty acid-induced insulin resistance in HepG2 hepatocytes through targeting JNK.
abstract: This study investigated the effects and molecular mechanisms of genistein in improving insulin resistance induced by free fatty acids (FFAs) in HepG2 hepatocytes. A model of insulin resistance in HepG2 cells was established by adding palmitic acid (0.5 mmol/L) to the culture medium and the cells were treated by genistein. Glucose consumption of HepG2 cells was determined by glucose oxidase method. The levels of c-jun N-terminal kinase (JNK) phosphorylation, insulin receptor substrate-1 (IRS-1) Ser307 phosphorylation, JNK, IRS-1, phosphatidylinositol-3-kinase p85 (PI-3K p85) and glucose transporter 1 (GLUT1) proteins were detected by Western blotting. The results showed that after the treatment with palmitic acid for 24 h, the insulin-stimulated glucose transport in HepG2 cells was inhibited, and the glucose consumption was substantially reduced. Meanwhile, the expressions of IRS-1, PI-3K p85 protein and GLUT1 were obviously reduced, while the levels of JNK phosphorylation and IRS-1 Ser307 phosphorylation and the expression of JNK protein were significantly increased, as compared with cells of normal control. However, the aforementioned indices, which indicated the existence of insulin resistance, were reversed by genistein at 1-4 μmol/L in a dose-dependent manner. It was concluded that insulin resistance induced by FFAs in HepG2 hepatocytes could be improved by genistein. Genistein might reverse FFAs-induced insulin resistance in HepG2 cells by targeting JNK.
authors.affiliation: Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.|Pharmacy College of Hubei University of Chinese Medicine, Wuhan, 430065, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Lei
authors.affiliation: Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. felu@tjh.tjmu.edu.cn.
authors.forename: Fu'er
authors.initials: F
authors.lastname: Lu
authors.affiliation: Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
authors.affiliation: Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Xu
authors.affiliation: Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Zhaoyi
authors.initials: Z
authors.lastname: Huang
mesh_terms: D005230:Fatty Acids, Nonesterified / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D048789:Phytoestrogens / Q000494:pharmacology
chemical_list: D005230:Fatty Acids, Nonesterified; D048789:Phytoestrogens; D019833:Genistein; D048670:MAP Kinase Kinase 4