PMID- 30260514
OWN - NLM
STAT- MEDLINE
DCOM- 20181029
LR  - 20181029
IS  - 1365-3083 (Electronic)
IS  - 0300-9475 (Linking)
VI  - 88
IP  - 5
DP  - 2018 Nov
TI  - Infliximab ameliorates tumor necrosis factor-alpha-induced insulin resistance by 
      attenuating PTP1B activation in 3T3L1 adipocytes in vitro.
PG  - e12716
LID - 10.1111/sji.12716 [doi]
AB  - Insulin resistance is the inability to respond to insulin and is considered a key 
      pathophysiological factor in the development of type 2 diabetes. Tumor necrosis 
      factor-alpha (TNF-alpha) can directly contribute to insulin resistance by 
      disrupting the insulin signalling pathway via protein-tyrosine phosphatase 1B 
      (PTP1B) activation, especially in adipocytes. Infliximab (Remicade((R)) ) is a 
      TNF-alpha-neutralizing antibody that has not been fully studied in insulin 
      resistance. We investigated the effect of infliximab on TNF-alpha-induced insulin 
      resistance in 3T3L1 adipocytes in vitro, and examined the possible molecular 
      mechanisms involved. Once differentiated, adipocytes were cultured with 
      5 mmol L(-1) 2-deoxy-D-glucose-(3) H and stimulated twice with 2 mumol L(-1) 
      insulin, in the presence or absence of 5 ng/mL TNF-alpha and/or 10 ng/mL 
      infliximab. Glucose uptake was measured every 20 minutes for 2 hour, and 
      phosphorylated forms of insulin receptor (IR), insulin receptor substrate-2 
      (IRS-2), protein kinase B (AKT) and PTP1B were determined by Western blotting. 
      TNF-alpha-treated adipocytes showed a significant 64% decrease in 
      insulin-stimulated glucose uptake as compared with control cells, whereas 
      infliximab reversed TNF-alpha actions by significantly improving glucose 
      incorporation. Although IR phosphorylation remained unaltered, TNF-alpha was able 
      to increase PTP1B activation and decrease phosphorylation of IRS-2 and AKT. 
      Notably, infliximab restored phosphorylation of IRS-2 and AKT by attenuating 
      PTP1B activation. This work demonstrates for the first time that infliximab 
      ameliorates TNF-alpha-induced insulin resistance in 3T3L1 adipocytes in vitro by 
      restoring the insulin signalling pathway via PTP1B inhibition. Further clinical 
      research is needed to determine the potential benefit of using infliximab for 
      treating insulin resistance in patients.
CI  - (c) 2018 The Foundation for the Scandinavian Journal of Immunology.
FAU - Mendez-Garcia, Lucia A
AU  - Mendez-Garcia LA
AD  - Laboratory for Proteomics and Metabolomics, Research Division, General Hospital 
      of Mexico "Dr. Eduardo Liceaga", Mexico City, Mexico.
FAU - Trejo-Millan, Fernanda
AU  - Trejo-Millan F
AD  - Laboratory for Proteomics and Metabolomics, Research Division, General Hospital 
      of Mexico "Dr. Eduardo Liceaga", Mexico City, Mexico.
FAU - Martinez-Reyes, Camilo P
AU  - Martinez-Reyes CP
AD  - Laboratory for Proteomics and Metabolomics, Research Division, General Hospital 
      of Mexico "Dr. Eduardo Liceaga", Mexico City, Mexico.
FAU - Manjarrez-Reyna, Aaron N
AU  - Manjarrez-Reyna AN
AD  - Laboratory for Proteomics and Metabolomics, Research Division, General Hospital 
      of Mexico "Dr. Eduardo Liceaga", Mexico City, Mexico.
FAU - Esquivel-Velazquez, Marcela
AU  - Esquivel-Velazquez M
AD  - Laboratory for Proteomics and Metabolomics, Research Division, General Hospital 
      of Mexico "Dr. Eduardo Liceaga", Mexico City, Mexico.
FAU - Melendez-Mier, Guillermo
AU  - Melendez-Mier G
AD  - Laboratory for Proteomics and Metabolomics, Research Division, General Hospital 
      of Mexico "Dr. Eduardo Liceaga", Mexico City, Mexico.
FAU - Islas-Andrade, Sergio
AU  - Islas-Andrade S
AD  - Laboratory for Proteomics and Metabolomics, Research Division, General Hospital 
      of Mexico "Dr. Eduardo Liceaga", Mexico City, Mexico.
FAU - Rojas-Bernabe, Araceli
AU  - Rojas-Bernabe A
AD  - Research Unit for Experimental Medicine, School of Medicine, National Autonomous 
      University of Mexico, Mexico City, Mexico.
FAU - Kzhyshkowska, Julia
AU  - Kzhyshkowska J
AD  - Department of Innate Immunity and Tolerance, Institute of Transfusion Medicine 
      and Immunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 
      Germany.
FAU - Escobedo, Galileo
AU  - Escobedo G
AUID- ORCID: 0000-0002-9224-7400
AD  - Laboratory for Proteomics and Metabolomics, Research Division, General Hospital 
      of Mexico "Dr. Eduardo Liceaga", Mexico City, Mexico.
LA  - eng
GR  - 295185-EULAMDIMA/Marie Curie International Research Staff Exchange Scheme/
GR  - 286209/Fondo Sectorial de Investigacion para la Educacion SEP-CONACYT-Mexico/
PT  - Journal Article
DEP - 20181010
PL  - England
TA  - Scand J Immunol
JT  - Scandinavian journal of immunology
JID - 0323767
RN  - 0 (Insulin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - B72HH48FLU (Infliximab)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1)
RN  - EC 3.1.3.48 (Ptpn1 protein, mouse)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/drug effects/*immunology/*metabolism
MH  - Animals
MH  - Enzyme Activation
MH  - Glucose/metabolism
MH  - Infliximab/*pharmacology
MH  - Insulin/pharmacology
MH  - Insulin Resistance/*immunology
MH  - Mice
MH  - Models, Biological
MH  - Phosphorylation
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 1/*metabolism
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/*metabolism/pharmacology
OTO - NOTNLM
OT  - Autoinmmunity
OT  - Cytokines
OT  - Diabetes
OT  - In Vitro
OT  - Inflammation
OT  - Molecules
OT  - Processes
OT  - Subject
EDAT- 2018/09/28 06:00
MHDA- 2018/10/30 06:00
CRDT- 2018/09/28 06:00
PHST- 2018/06/12 00:00 [received]
PHST- 2018/08/27 00:00 [revised]
PHST- 2018/09/02 00:00 [accepted]
PHST- 2018/09/28 06:00 [pubmed]
PHST- 2018/10/30 06:00 [medline]
PHST- 2018/09/28 06:00 [entrez]
AID - 10.1111/sji.12716 [doi]
PST - ppublish
SO  - Scand J Immunol. 2018 Nov;88(5):e12716. doi: 10.1111/sji.12716. Epub 2018 Oct 10.