title: CtBP2 ameliorates palmitate-induced insulin resistance in HepG2 cells through ROS mediated JNK pathway.
abstract: Oxidative stress plays a significant role in the development of hepatic insulin resistance, but the underlying molecular mechanisms remain poorly understood. In this study, we discovered that C-terminal-binding protein 2 (CtBP2) level was decreased in insulin resistance. Taking into account the relationship between CtBP family protein (ANGUSTIFOLIA) and reactive oxygen species (ROS) accumulation, we conjectured CtBP2 was involved in insulin resistance through ROS induced stress. In order to verify this hypothesis, we over-expressed CtBP2 in palmitate (PA) treated HepG2 cells. Here, we found that over-expression of CtBP2 ameliorated insulin sensitivity by increasing phosphorylation of glycogen synthase kinase 3β (GSK3β) and protein kinase B (AKT). These data suggest that CtBP2 plays a critical role in the development of insulin resistance. Moreover, CtBP2 reversed the effects of PA on ROS level, lipid accumulation, hepatic glucose uptake and gluconeogenesis. We also found that over-expression of CtBP2 could suppress PA induced c-jun NH2 terminal kinase (JNK) activation. Furthermore, JNK inhibitor SP600125 was shown to promote the effect of CtBP2 on insulin signaling. Thus, we demonstrated that CtBP2 ameliorated PA-induced insulin resistance via ROS-dependent JNK pathway.
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Pingli
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, the Second People's Hospital of Changzhou City, 29 Xinglong Lane, Changzhou 213000, Jiangsu Province, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Shi
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Cang
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Jieru
authors.initials: J
authors.lastname: Huang
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wu
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yan
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, People's Republic of China. Electronic address: swfenmi6@126.com.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Cui
authors.affiliation: Department of Endocrinology, the Second People's Hospital of Changzhou City, 29 Xinglong Lane, Changzhou 213000, Jiangsu Province, People's Republic of China. Electronic address: 0818yezi@163.com.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Ye
mesh_terms: D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D056970:Co-Repressor Proteins; D015536:Down-Regulation / Q000187:drug effects; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007333:Insulin Resistance; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010168:Palmitates / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D056970:Co-Repressor Proteins; D009419:Nerve Tissue Proteins; D010168:Palmitates; D017382:Reactive Oxygen Species; D000429:Alcohol Oxidoreductases; C421248:CTBP2 protein, human; D048031:JNK Mitogen-Activated Protein Kinases; D005947:Glucose
keywords: CtBP2; HepG2 cells; Insulin resistance; JNK; Oxidative stress