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The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance
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 modifi...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613339/ https://www.ncbi.nlm.nih.gov/pubmed/26402673 http://dx.doi.org/10.3390/ijms160922856 |
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author | Zhao, Yun Tang, Zhuqi Shen, Aiguo Tao, Tao Wan, Chunhua Zhu, Xiaohui Huang, Jieru Zhang, Wanlu Xia, Nana Wang, Suxin Cui, Shiwei Zhang, Dongmei |
author_facet | Zhao, Yun Tang, Zhuqi Shen, Aiguo Tao, Tao Wan, Chunhua Zhu, Xiaohui Huang, Jieru Zhang, Wanlu Xia, Nana Wang, Suxin Cui, Shiwei Zhang, Dongmei |
author_sort | Zhao, Yun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4613339 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-46133392015-10-26 The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance Zhao, Yun Tang, Zhuqi Shen, Aiguo Tao, Tao Wan, Chunhua Zhu, Xiaohui Huang, Jieru Zhang, Wanlu Xia, Nana Wang, Suxin Cui, Shiwei Zhang, Dongmei Int J Mol Sci Article 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. MDPI 2015-09-22 /pmc/articles/PMC4613339/ /pubmed/26402673 http://dx.doi.org/10.3390/ijms160922856 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhao, Yun Tang, Zhuqi Shen, Aiguo Tao, Tao Wan, Chunhua Zhu, Xiaohui Huang, Jieru Zhang, Wanlu Xia, Nana Wang, Suxin Cui, Shiwei Zhang, Dongmei The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance |
title | The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance |
title_full | The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance |
title_fullStr | The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance |
title_full_unstemmed | The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance |
title_short | The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance |
title_sort | role of ptp1b o-glcnacylation in hepatic insulin resistance |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613339/ https://www.ncbi.nlm.nih.gov/pubmed/26402673 http://dx.doi.org/10.3390/ijms160922856 |
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