Tumor necrosis factor-alpha-induced insulin resistance in adipocytes.
Recent studies examining the link between insulin resistance and the development of obesity and noninsulin-dependent diabetes mellitus are consistent with the involvement of tumor necrosis factor-alpha (TNF-alpha) as a central mediator. In insulin resistant obese mouse models, neutralization of TNF-alpha in circulation has been demonstrated to restore insulin-mediated glucose uptake. Adipose tissue has been shown to be a site for synthesis of TNF-alpha, with the degree of adiposity directly correlated with the level of synthesis. Studies conducted on obese human patients have demonstrated a correlation between levels of TNF-alpha, the extent of obesity, as well as the level of hyperinsulinemia observed. Mechanistic studies in cell culture have suggested that TNF-alpha functions to render cells insulin resistant through regulation of the synthesis of the insulin responsive glucose transporter as well as through interference with insulin signaling. This review will address these issues and additionally introduce the reader to the molecular aspects of TNF-alpha, its receptors as well as TNF-alpha-initiated signaling cascades, that are necessary to understand the function of this cytokine in the regulation of adipose tissue metabolism.
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Department of Biochemistry, School of Medicine, East Carolina University, Greenville, North Carolina 27858, USA.
Pekala
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D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D051275:Glucose Transporter Type 4; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis; D009124:Muscle Proteins; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D016877:Oxidants; C495692:SLC2A4 protein, human; C495693:Slc2a4 protein, mouse; D014409:Tumor Necrosis Factor-alpha