title: PCBP2 regulates hepatic insulin sensitivity via HIF-1α and STAT3 pathway in HepG2 cells.
abstract: Elevated free fatty acids (FFAs) are fundamental to the pathogenesis of hepatic insulin resistance. However, the molecular mechanisms of insulin resistance remain not completely understood. Transcriptional dysregulation, post-transcriptional modifications and protein degradation contribute to the pathogenesis of insulin resistance. Poly(C) binding proteins (PCBPs) are RNA-binding proteins that are involved in post-transcriptional control pathways. However, there are little studies about the roles of PCBPs in insulin resistance. PCBP2 is the member of the RNA-binding proteins and is thought to participate in regulating hypoxia inducible factor-1 (HIF-1α) and signal transducers and activators of transcription (STAT) pathway which are involved in regulating insulin signaling pathway. Here, we investigated the influence of PCBP2 on hepatic insulin resistance. We showed that the protein and mRNA levels of PCBP2 were down-regulated under insulin-resistant conditions. In addition, we showed that over-expression of PCBP2 ameliorates palmitate (PA)-induced insulin resistance, which was indicated by elevated phosphorylation of protein kinase B (AKT) and glycogen synthase kinase 3β (GSK3β). We also found that over-expression of PCBP2 inhibits HIF1α and STAT3 pathway. Furthermore, glucose uptake was found to display a similar tendency with the phosphorylation of Akt. The expressions of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), two key gluconeogenic enzymes, were down-regulated following Over-expression of PCBP2. Accordingly, PA-induced intracellular lipid accumulation was suppressed in over-expression of PCBP2 HepG2 cells. In addition, we found that over-expression of PCBP2 inhibits HIF1α and STAT3 pathway. Our results demonstrate that PCBP2 was involved in hepatic insulin sensitivity might via HIF-1α and STAT3 pathway in HepG2 cells.
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Nana
authors.initials: N
authors.lastname: Xia
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, People's Republic of China; Department of Endocrinology and Metabolic Disease, First Affiliated Hospital of Soochow University, 188 Shizi Street, Soochow 215006, Jiangsu Province, People's Republic of China.
authors.forename: Zhuqi
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Cuifang
authors.initials: C
authors.lastname: Wang
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; Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Guangfei
authors.initials: G
authors.lastname: Xu
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; Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Nie
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Wanlu
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, People's Republic of China.
authors.forename: Suxin
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, People's Republic of China. Electronic address: neizhuhui@163.com.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, People's Republic of China. Electronic address: wfcnei@163.com.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Cui
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D015536:Down-Regulation; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D056945:Hep G2 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019308:Palmitic Acid / Q000494:pharmacology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C501903:PCBP2 protein, human; C501904:Pcbp2 protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D019308:Palmitic Acid; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D005947:Glucose
keywords: HIF1α; HepG2 cells; Insulin resistance; PCBP2; STAT3