title: The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance.
abstract: Protein tyrosine phosphatase 1B (PTP1B), which can directly dephosphorylate both the insulin receptor and insulin receptor substrate 1 (IRS-1), thereby terminating insulin signaling, reportedly plays an important role in insulin resistance. Accumulating evidence has demonstrated that O-GlcNAc modification regulates functions of several important components of insulin signal pathway. In this study, we identified that PTP1B is modified by O-GlcNAcylation at three O-GlcNAc sites (Ser104, Ser201, and Ser386). Palmitate acid (PA) impaired the insulin signaling, indicated by decreased phosphorylation of both serine/threonine-protein kinase B (Akt) and glycogen synthase kinase 3 beta (GSK3β) following insulin administration, and upregulated PTP1B O-GlcNAcylation in HepG2 cells. Compared with the wild-type, intervention PTP1B O-GlcNAcylation by site-directed gene mutation inhibited PTP1B phosphatase activity, resulted in a higher level of phosphorylated Akt and GSK3β, recovered insulin sensitivity, and improved lipid deposition in HepG2 cells. Taken together, our research showed that O-GlcNAcylation of PTP1B can influence insulin signal transduction by modulating its own phosphatase activity, which participates in the process of hepatic insulin resistance.
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, Nantong 226001, China. zhaoyunnt@163.com.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, China. zhaoyunnt@163.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, Nantong 226001, China. tangzhuqi@aliyun.com.
authors.forename: Zhuqi
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, China. shag@ntu.edu.cn.|Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China. shag@ntu.edu.cn.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Shen
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, China. nttaotao@ntu.edu.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, China. zhao1027601171@163.com.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Wan
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, Nantong 226001, China. neizhuhui@163.com.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, Nantong 226001, China. liangchenyinuan@126.com.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, China. liangchenyinuan@126.com.
authors.forename: Jieru
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, Nantong 226001, China. wang496369@163.com.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, China. wang496369@163.com.
authors.forename: Wanlu
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, Nantong 226001, China. 15851209084@163.com.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, China. 15851209084@163.com.
authors.forename: Nana
authors.initials: N
authors.lastname: Xia
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, Nantong 226001, China. wangsuxin2009@sina.com.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, China. wangsuxin2009@sina.com.
authors.forename: Suxin
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, Nantong 226001, China. shiweicui911@163.com.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Cui
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, China. zdm@ntu.edu.cn.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000215:Acylation; D056945:Hep G2 Cells; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism*
chemical_list: C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D000117:Acetylglucosamine
keywords: O-GlcNAc; PTP1B; insulin resistance