Protein phosphatase 4 (PP4) functions as a critical regulator in tumor necrosis factor (TNF)-α-induced hepatic insulin resistance

Protein phosphatase 4 (PP4) was shown to participate in multiple cellular processes, including DNA damage response, cell cycle and embryo development. Recent studies demonstrated a looming role of PP4 in glucose metabolism. However, whether PP4 is involved in hepatic insulin resistance remains poorl...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2015-12, Vol.5 (1), p.18093-18093, Article 18093
Main Authors: Zhao, Hongye, Huang, Xiuqing, Jiao, Juan, Zhang, Hangxiang, Liu, Jin, Qin, Weiwei, Meng, Xiangyu, Shen, Tao, Lin, Yajun, Chu, Jiaojiao, Li, Jian
Format: Article
Language:English
Subjects:
Animals
Blotting, Western
Cells, Cultured
Gene Expression - drug effects
Hep G2 Cells
Hepatocytes - drug effects
Hepatocytes - metabolism
Humans
Insulin Receptor Substrate Proteins - genetics
Insulin Receptor Substrate Proteins - metabolism
Insulin Resistance
Liver - drug effects
Liver - metabolism
Liver - physiopathology
Mice, Inbred C57BL
Phosphoprotein Phosphatases - genetics
Phosphoprotein Phosphatases - metabolism
Phosphorylation - drug effects
Reverse Transcriptase Polymerase Chain Reaction
RNA Interference
Tumor Necrosis Factor-alpha - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Protein phosphatase 4 (PP4) was shown to participate in multiple cellular processes, including DNA damage response, cell cycle and embryo development. Recent studies demonstrated a looming role of PP4 in glucose metabolism. However, whether PP4 is involved in hepatic insulin resistance remains poorly understood. The objective of this study was to estimate the role of PP4 in tumor necrosis factor (TNF)-α-induced hepatic insulin resistance. db/db mice and TNF-α-treated C57BL/6J mice were used as hepatic insulin resistance animal models. In vitro models were established in both HepG2 cells and primary hepatocytes by TNF-α treatment. We found that increased expression and activity of PP4 occurred in the livers of db/db mice and TNF-α-induced hepatic insulin resistance both in vitro and in vivo. Actually, PP4 silencing and suppression of PP4 activity ameliorated TNF-α-induced hepatic insulin resistance, whereas over-expression of PP4 caused insulin resistance. We then further investigated the prodiabetic mechanism of PP4 in TNF-α-induced insulin resistance. We found that PP4 formed a complex with IRS-1 to promote phosphorylation of IRS-1 on serine 307 via JNK activation and reduce the expression of IRS-1. Thus, PP4 is an important regulator in inflammatory related insulin resistance.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep18093