抄録
Recent studies have indicated that tumor necrosis factor (TNF)-α plays a significant role in insulin resistance. It has been proposed that selective impairment of insulin signaling in glucose metabolism is related to the development of atherosclerosis, although the mechanisms are not clear. The aim of this study was to elucidate the effect of TNF-α on tissue specificity and selectivity to insulin signaling. L6 myotubes and rat aortic vascular smooth muscle cells (VSMC) were cultured. Cells were stimulated with insulin pretreated with or without TNF-α. The protein extracts were used for electrophoresis and immunoblotting studies to examine phosphorylation of insulin receptor (IR)-β, insulin receptor substrate (IRS)-1 and extracellular signal-regulated kinase (ERK). IR-β phosphorylation was not affected by TNF-α in L6 or in VSMC. TNF-α significantly (p <0.05) inhibited IRS-1 phosphorylation by insulin but had no effect on ERK in L6. TNF-α had no effect on either IRS-1 phosphorylation or ERK in VSMC. Insulin induced ERK phosphorylation in a dose-dependent manner in VSMC. These results suggests that TNF-α plays a significant role in the tissue specificity and signal selectivity of insulin resistance. The pathway related to glucose metabolism is selectively impaired by TNF-α in skeletal muscle, and this impairment may induce compensatory hyperinsulinemia, which in turn would stimulate the pathway related to the cell proliferation in vascular tissues and possibly enhance the progression of atherosclerosis. (Hypertens Res 2003; 26: 389-396)
