It has been hypothesized that increased production of tumor necrosis factor-alpha (TNF-alpha) plays a role in causing the insulin resistance associated with obesity. Obesity with insulin resistance is associated with increased production of TNF-alpha by fat cells. Exposure of 3T3-L1 adipocytes to TNF-alpha for 3-4 days makes them insulin resistant. TNF-alpha has also been reported to rapidly (15-60 min) cause insulin resistance, with a decrease in insulin-stimulated tyrosine phosphorylation, in a number of cultured cell lines. Because skeletal muscle is the major tissue responsible for insulin-stimulated glucose disposal, we performed the present study to determine if acute exposure to TNF-alpha causes insulin resistance in muscle. We found that exposure of soleus muscles to 6 nmol/l TNF-alpha for 45 min in vitro had no inhibitory effect on insulin-stimulated tyrosine phosphorylation of the insulin receptor or insulin receptor substrate 1 (IRS-1) or on phosphatidylinositol 3-kinase association with IRS-1. Incubation of epitrochlearis and soleus muscles with 6 nmol/l TNF-alpha for 45 min or 4 h had no effect on insulin-stimulated 2-deoxyglucose (2-DG) uptake. Treatment of epitrochlearis muscles with 2 nmol/l TNF-alpha for 8 h also had no effect on insulin-stimulated 2-DG uptake. We conclude that in contrast to Fao hepatoma cells and 3T3-L1 fibroblasts, skeletal muscle does not become insulin resistant in response to short-term exposure to TNF-alpha.
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Abstract|
May 01 1998
Short-term exposure to tumor necrosis factor-alpha does not affect insulin-stimulated glucose uptake in skeletal muscle. Free
L A Nolte;
L A Nolte
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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P A Hansen;
P A Hansen
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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M M Chen;
M M Chen
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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J M Schluter;
J M Schluter
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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E A Gulve;
E A Gulve
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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J O Holloszy
J O Holloszy
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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Citation
L A Nolte, P A Hansen, M M Chen, J M Schluter, E A Gulve, J O Holloszy; Short-term exposure to tumor necrosis factor-alpha does not affect insulin-stimulated glucose uptake in skeletal muscle.. Diabetes 1 May 1998; 47 (5): 721–726. https://doi.org/10.2337/diabetes.47.5.721
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