title: PRDX1 is involved in palmitate induced insulin resistance via regulating the activity of p38MAPK in HepG2 cells.
abstract: Studies have identified that type 2 diabetes mellitus (T2DM) patients displayed higher levels of plasma peroxiredoxin1(PRDX1) than non-diabetics. However, the impact of PRDX1 on insulin resistance and the underlying mechanism remains totally unknown. Here, we investigated the influence of PRDX1 on hepatic insulin resistance. We showed that the protein and mRNA levels of PRDX1 were significantly elevated under insulin-resistant conditions. In addition, we showed that interference of PRDX1 ameliorated palmitate-induced insulin resistance in HepG2 cells, which was indicated by elevated phosphorylation of protein kinase B (AKT) and of glycogen synthase kinase-3 (GSK3β). Furthermore, the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), two key gluconeogenic enzymes, were down-regulated following PRDX1 depletion. Accordingly, glucose uptake was suppressed in PRDX1-interferred HepG2 cells. In addition, Over-expression of PRDX1 enhanced PA-induced insulin resistance in HepG2 cells. Moreover, we found that knocking down PRDX1 improves insulin sensitivity and decreased the activation of p38 mitogen-activated protein kinase (p38MAPK). Our results demonstrate that PRDX1 can induce hepatic insulin resistance by activating p38MAPK signaling and identifies potential targets for new treatments.
authors: Department of Endocrinology and Metabolic Disease, First Affiliated Hospital of Soochow University, 188 Shizi Street, Soochow 215006, Jiangsu Province, PR China; Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, PR China.
authors: Zhuqi
authors: Z
authors: Tang
authors: Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, PR China.
authors: Nana
authors: N
authors: Xia
authors: Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, PR China.
authors: Xinlu
authors: X
authors: Yuan
authors: Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, PR China.
authors: Xiaohui
authors: X
authors: Zhu
authors: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, PR China.
authors: Guangfei
authors: G
authors: Xu
authors: Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, PR China.
authors: Shiwei
authors: S
authors: Cui
authors: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, PR China.
authors: Tingting
authors: T
authors: Zhang
authors: Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, PR China.
authors: Wanlu
authors: W
authors: Zhang
authors: Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, PR China.
authors: Yun
authors: Y
authors: Zhao
authors: Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, PR China.
authors: Suxin
authors: S
authors: Wang
authors: Department of Endocrinology and Metabolic Disease, First Affiliated Hospital of Soochow University, 188 Shizi Street, Soochow 215006, Jiangsu Province, PR China. Electronic address: bimins@163.com.
authors: Bimin
authors: B
authors: Shi
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D010168:Palmitates / Q000378:metabolism; D054464:Peroxiredoxins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D010168:Palmitates; D012333:RNA, Messenger; C515940:PRDX1 protein, human; D054464:Peroxiredoxins; C489899:Prdx1 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose
keywords: HepG2; Insulin resistance; PRDX1; p38MAPK