The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance
AbstractProtein 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. View Full-Text
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Zhao, Y.; Tang, Z.; Shen, A.; Tao, T.; Wan, C.; Zhu, X.; Huang, J.; Zhang, W.; Xia, N.; Wang, S.; Cui, S.; Zhang, D. The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance. Int. J. Mol. Sci. 2015, 16, 22856-22869.
Zhao Y, Tang Z, Shen A, Tao T, Wan C, Zhu X, Huang J, Zhang W, Xia N, Wang S, Cui S, Zhang D. The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance. International Journal of Molecular Sciences. 2015; 16(9):22856-22869.Chicago/Turabian Style
Zhao, Yun; Tang, Zhuqi; Shen, Aiguo; Tao, Tao; Wan, Chunhua; Zhu, Xiaohui; Huang, Jieru; Zhang, Wanlu; Xia, Nana; Wang, Suxin; Cui, Shiwei; Zhang, Dongmei. 2015. "The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance." Int. J. Mol. Sci. 16, no. 9: 22856-22869.