PMID- 24186864
OWN - NLM
STAT- MEDLINE
DCOM- 20140328
LR  - 20220129
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Linking)
VI  - 63
IP  - 2
DP  - 2014 Feb
TI  - Myeloid-cell protein tyrosine phosphatase-1B deficiency in mice protects against 
      high-fat diet and lipopolysaccharide-induced inflammation, hyperinsulinemia, and 
      endotoxemia through an IL-10 STAT3-dependent mechanism.
PG  - 456-70
LID - 10.2337/db13-0885 [doi]
AB  - Protein tyrosine phosphatase-1B (PTP1B) negatively regulates insulin and leptin 
      signaling, rendering it an attractive drug target for treatment of 
      obesity-induced insulin resistance. However, some studies suggest caution when 
      targeting macrophage PTP1B, due to its potential anti-inflammatory role. We 
      assessed the role of macrophage PTP1B in inflammation and whole-body metabolism 
      using myeloid-cell (LysM) PTP1B knockout mice (LysM PTP1B). LysM PTP1B mice were 
      protected against lipopolysaccharide (LPS)-induced endotoxemia and hepatic damage 
      associated with decreased proinflammatory cytokine secretion in vivo. In vitro, 
      LPS-treated LysM PTP1B bone marrow-derived macrophages (BMDMs) displayed 
      increased interleukin (IL)-10 mRNA expression, with a concomitant decrease in 
      TNF-alpha mRNA levels. These anti-inflammatory effects were associated with increased 
      LPS- and IL-10-induced STAT3 phosphorylation in LysM PTP1B BMDMs. Chronic 
      inflammation induced by high-fat (HF) feeding led to equally beneficial effects 
      of macrophage PTP1B deficiency; LysM PTP1B mice exhibited improved glucose and 
      insulin tolerance, protection against LPS-induced hyperinsulinemia, decreased 
      macrophage infiltration into adipose tissue, and decreased liver damage. HF-fed 
      LysM PTP1B mice had increased basal and LPS-induced IL-10 levels, associated with 
      elevated STAT3 phosphorylation in splenic cells, IL-10 mRNA expression, and 
      expansion of cells expressing myeloid markers. These increased IL-10 levels 
      negatively correlated with circulating insulin and alanine transferase levels. 
      Our studies implicate myeloid PTP1B in negative regulation of 
      STAT3/IL-10-mediated signaling, highlighting its inhibition as a potential 
      anti-inflammatory and antidiabetic target in obesity.
FAU - Grant, Louise
AU  - Grant L
AD  - Institute of Medical Sciences, University of Aberdeen, College of Life Sciences 
      and Medicine, Foresterhill Health Campus, Aberdeen, United Kingdom.
FAU - Shearer, Kirsty D
AU  - Shearer KD
FAU - Czopek, Alicja
AU  - Czopek A
FAU - Lees, Emma K
AU  - Lees EK
FAU - Owen, Carl
AU  - Owen C
FAU - Agouni, Abdelali
AU  - Agouni A
FAU - Workman, James
AU  - Workman J
FAU - Martin-Granados, Cristina
AU  - Martin-Granados C
FAU - Forrester, John V
AU  - Forrester JV
FAU - Wilson, Heather M
AU  - Wilson HM
FAU - Mody, Nimesh
AU  - Mody N
FAU - Delibegovic, Mirela
AU  - Delibegovic M
LA  - eng
GR  - ETM/351/CSO_/Chief Scientist Office/United Kingdom
GR  - PG/11/8/28703/BHF_/British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131101
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Dietary Fats)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 2.7.10.2 (Janus Kinases)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adipose Tissue, White/drug effects/pathology
MH  - Animals
MH  - Cell Line
MH  - Chemical and Drug Induced Liver Injury
MH  - Dietary Fats/*adverse effects
MH  - Endotoxemia/chemically induced
MH  - Gene Expression Regulation, Enzymologic/physiology
MH  - Glucose/metabolism
MH  - Homeostasis
MH  - Hyperinsulinism/*chemically induced
MH  - Inflammation/*chemically induced/pathology
MH  - Interleukin-10/genetics/metabolism
MH  - Janus Kinases/genetics/metabolism
MH  - Lipopolysaccharides/*toxicity
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Myeloid Cells/*enzymology/physiology
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 1/genetics/*metabolism
MH  - STAT3 Transcription Factor/genetics/metabolism
MH  - Signal Transduction
MH  - Spleen/cytology/metabolism
EDAT- 2013/11/05 06:00
MHDA- 2014/03/29 06:00
CRDT- 2013/11/05 06:00
PHST- 2013/11/05 06:00 [entrez]
PHST- 2013/11/05 06:00 [pubmed]
PHST- 2014/03/29 06:00 [medline]
AID - db13-0885 [pii]
AID - 10.2337/db13-0885 [doi]
PST - ppublish
SO  - Diabetes. 2014 Feb;63(2):456-70. doi: 10.2337/db13-0885. Epub 2013 Nov 1.