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Horm Metab Res 2010; 42(2): 115-121
DOI: 10.1055/s-0029-1241834
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

TNF-α Inhibits Insulin Action in Liver and Adipose Tissue: A Model of Metabolic Syndrome

S. S. Solomon1 , 2 , 3 , O. Odunusi1 , 2 , D. Carrigan1 , 2 , G. Majumdar1 , 2 , D. Kakoola1 , 2 , N. I. Lenchik1 , 2 , I. C. Gerling1 , 2
  • 1Department of Medicine, University of Tennessee Health Science Center, Veterans Affairs Medical Center, Memphis, Tennessee, USA
  • 2University of Tennessee Research Service, Veterans Affairs Medical Center, Memphis, Tennessee, USA
  • 3Department of Pharmacology, University of Tennessee Health Science Center, Veterans Affairs Medical Center, Memphis, Tennessee, USA
Weitere Informationen

Publikationsverlauf

received 29.06.2009

accepted 07.10.2009

Publikationsdatum:
03. Dezember 2009 (online)

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Abstract

Several studies suggest that TNF-α contributes to the development of insulin resistance (IR). We compared transcriptional profiles of rat H-411E liver cells exposed to insulin in the absence or presence of TNF-α. We identified 33 genes whose expression was altered by insulin, and then reversed by TNF-α. Twenty-six of these 33 genes created a single network centered around: insulin, TNF-α, p38-MAPK, TGFb1; SMAD and STAT1; and enzymes and cytokines involved in apoptosis (CASP3, GADD45B, IL2, TNF-α, etc.). We analyzed our data together with other data of gene expression in adipocytes and found a number of processes common to both, for example, cell death and inflammation; intercellular signaling and metabolism; G-Protein, IL-10 and PTEN signaling. Moreover, the two datasets combined generated a single molecular network that further identified PTEN (a phosphatase) as a unique new link between insulin signaling, IR, and apoptosis reflecting the pathophysiology of “metabolic syndrome”.

Key words

metabolic syndrome model - liver cells - tissue culture - genomics - insulin - receptor and signaling - phosphorylation - energy utilization - apoptosis

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Correspondence

S. S. SolomonMD 

Division of Endocrinology University of Tennessee Health Science Center

VAMC Research 151

1030 Jefferson Avenue

TN 38104 Memphis

USA

Telefon: +1 901 577 7274

Fax: +1 901 577 7273

eMail: ssolomon@utmem.edu