期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 16, 期 9, 页码 22856-22869出版社
MDPI AG
DOI: 10.3390/ijms160922856
关键词
insulin resistance; PTP1B; O-GlcNAc
资金
- National Science Foundation of China [31500647]
- Natural Science Foundation of the Jiangsu Higher Education Institutions of China [15KJA310003]
- Natural Science Foundation of Jiangsu Province [BK20150408]
- Technology Innovation Program of Nantong University [YKS14021]
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 (GSK3) 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 GSK3, 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.
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