Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhao, Yun, Tang, Zhuqi, Shen, Aiguo, Tao, Tao, Wan, Chunhua, Zhu, Xiaohui, Huang, Jieru, Zhang, Wanlu, Xia, Nana, Wang, Suxin, Cui, Shiwei, Zhang, Dongmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
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
_version_ 1782396263498514432
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
work_keys_str_mv AT zhaoyun theroleofptp1boglcnacylationinhepaticinsulinresistance
AT tangzhuqi theroleofptp1boglcnacylationinhepaticinsulinresistance
AT shenaiguo theroleofptp1boglcnacylationinhepaticinsulinresistance
AT taotao theroleofptp1boglcnacylationinhepaticinsulinresistance
AT wanchunhua theroleofptp1boglcnacylationinhepaticinsulinresistance
AT zhuxiaohui theroleofptp1boglcnacylationinhepaticinsulinresistance
AT huangjieru theroleofptp1boglcnacylationinhepaticinsulinresistance
AT zhangwanlu theroleofptp1boglcnacylationinhepaticinsulinresistance
AT xianana theroleofptp1boglcnacylationinhepaticinsulinresistance
AT wangsuxin theroleofptp1boglcnacylationinhepaticinsulinresistance
AT cuishiwei theroleofptp1boglcnacylationinhepaticinsulinresistance
AT zhangdongmei theroleofptp1boglcnacylationinhepaticinsulinresistance
AT zhaoyun roleofptp1boglcnacylationinhepaticinsulinresistance
AT tangzhuqi roleofptp1boglcnacylationinhepaticinsulinresistance
AT shenaiguo roleofptp1boglcnacylationinhepaticinsulinresistance
AT taotao roleofptp1boglcnacylationinhepaticinsulinresistance
AT wanchunhua roleofptp1boglcnacylationinhepaticinsulinresistance
AT zhuxiaohui roleofptp1boglcnacylationinhepaticinsulinresistance
AT huangjieru roleofptp1boglcnacylationinhepaticinsulinresistance
AT zhangwanlu roleofptp1boglcnacylationinhepaticinsulinresistance
AT xianana roleofptp1boglcnacylationinhepaticinsulinresistance
AT wangsuxin roleofptp1boglcnacylationinhepaticinsulinresistance
AT cuishiwei roleofptp1boglcnacylationinhepaticinsulinresistance
AT zhangdongmei roleofptp1boglcnacylationinhepaticinsulinresistance