Hormone and Metabolic Research · 2009 · 38 citations · 0 references
Life SciencesEndocrinologyMolecular BiologyApoptosisGene ExpressionSignal TransductionAdipose TissueApoptosis RegulationApoptotic SignalingInsulin ResistanceMetabolic SignalingMetabolic SyndromeAdipocyte Insulin SignalingAdipose Tissue DysfunctionInsulin Signal TransductionInsulin SignalingInsulin Signaling Gene ExpressionInsulin Signaling PathwayLiver Insulin SignalingPten Signaling
Several studies suggest that TNF-alpha 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-alpha. We identified 33 genes whose expression was altered by insulin, and then reversed by TNF-alpha. Twenty-six of these 33 genes created a single network centered around: insulin, TNF-alpha, p38-MAPK, TGFb1; SMAD and STAT1; and enzymes and cytokines involved in apoptosis (CASP3, GADD45B, IL2, TNF-alpha, 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".