The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance

International Journal of Molecular Sciences

Yun Zhao¹  Zhuqi Tang¹  Aiguo Shen²  Tao Tao²  Chunhua Wan²  Xiaohui Zhu¹  Jieru Huang¹  Wanlu Zhang¹  Nana Xia¹  Suxin Wang¹  Shiwei Cui¹  Dongmei Zhang² 

[1] Department of Endocrinology, Affiliated Hospital of Nantong University, Nantong 226001, China; E-Mails:;Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, China; E-Mails:

关键词: insulin resistance;    PTP1B;    O-GlcNAc;   

DOI  :  10.3390/ijms160922856

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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© 2015 by the authors; licensee MDPI, Basel, Switzerland.