Nuclear factor kappa B impairs insulin signaling pathway in skeletal muscle cells of rat with sepsis / 中华外科杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of nuclear factor kappa B (NF-kappaB) on insulin signaling in skeletal muscle cells of rat with sepsis.</p><p><b>METHODS</b>SD rats were randomly divided into two groups control group and sepsis group.Sepsis model was reproduced by cecal ligation and puncture in sepsis group. At 8, 16, 24, 48 and 72 h after operation, the gastrocnemius was harvested. Conventional HE staining was used to observe the morphology of skeletal muscle cells. IRS-1 protein and tyrosine phosphorylation of IRS-1 and Ser(307) phosphorylation of IRS-1 were detected by Western Blotting and immuno-precipitation. Activities of NF-kappaB in skeletal muscle cells were detected by electrophoretic mobility shift assay.</p><p><b>RESULTS</b>Tyrosine phosphorylation of IRS-1 in sepsis group was significantly lower than in control group (P < 0.01), while Ser(307) phosphorylation of IRS-1 in sepsis group was significantly higher than in control group (P < 0.01). In sepsis group, NF-kappaB activity in skeletal muscle cells was significantly higher than in control group (P < 0.01). There was significant negative correlation between activity of NF-kappaB and tyrosine phosphorylation of IRS-1 (r = 0.972, P < 0.01). There was significant positive correlation between activities of NF-kappaB and Ser(307) phosphorylation of IRS-1 (r = 0.969, P < 0.01).</p><p><b>CONCLUSIONS</b>There is no inflammatory cell infiltrate in skeletal muscle cells with sepsis. But the activity of NF-kappaB in skeletal muscle cells is obviously enhanced, and it is closely related with disorder of insulin signaling in skeletal muscle cells of rat with sepsis.</p>