Clinical and experimental studies have implicated high circulating levels of the cytokine tumour necrosis factor-α (TNF-α) in the pathogenesis of insulin resistance, not only in obesity and diabetes, but also in clinical conditions associated with cachexia and sepsis. TNF-α impairs insulin-mediated glucose uptake in adipocytes, but because of lipolytic effects the interpretation of clinical studies and the extent to which TNF-α affects muscle insulin sensitivity are unclear. In addition, protein kinase C (PKC) has recently been implicated in the mechanism of TNF-α-induced insulin resistance. The present study investigated the effects of TNF-α and a PKC inhibitor (RO-318220) on basal and insulin-stimulated 2-[3H]deoxyglucose uptake in cultured L6 myoblasts. Reverse transcriptase–PCR analysis confirmed that L6 myoblasts express TNF-α receptors I and II (p60 and p80). Dose–response curves for glucose uptake were fitted to a quadratic function to derive CI-150 values (concentration of insulin required to increase glucose uptake by 50%). Incubation with TNF-α at 1 or 10 ng/ml for 24 h had no significant effect on basal glucose uptake, insulin sensitivity or maximal insulin responsiveness. CI-150 values (means±S.E.M.) were as follows: basal, 91.2±13 nM; 1 ng/ml TNF-α, 102±12 nM; and basal, 70.8±13 nM; 10 ng/ml TNF-α, 43.7±40 nM. PKC inhibition markedly attenuated glucose uptake, but there was no difference in insulin sensitivity with RO-318220 alone compared with RO-318220+TNF-α. In conclusion, although increased TNF-α expression and plasma concentrations have been implicated in the pathogenesis of insulin resistance in various clinical states, there is no evidence that TNF-α impairs insulin-stimulated glucose uptake in a skeletal-muscle-derived cell line.
Effects of tumour necrosis factor-α and inhibition of protein kinase C on glucose uptake in L6 myoblasts
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Divina PATIAG, Samuel GRAY, Iskander IDRIS, Richard DONNELLY; Effects of tumour necrosis factor-α and inhibition of protein kinase C on glucose uptake in L6 myoblasts. Clin Sci (Lond) 1 October 2000; 99 (4): 303–307. doi: https://doi.org/10.1042/cs0990303
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