Aim: This study aimed to investigate whether NF-κB contributes to insulin resistance in type 2 diabetes (T2DM).
Methods: Subcutaneous abdominal adipose tissue was obtained from T2DM patients and non-diabetic control subjects. Pre-adipocytes were cultured and differentiated into adipocytes in vitro. Upon insulin stimulation, IRS-1 tyrosine and AKT (Ser473) phosphorylation were examined by immunoprecipitation and immunoblotting, while levels of inflammatory mediators IL-6 and MCP-1, and the DNA-binding activity of NF-κB, were examined by ELISA and electrophoretic mobility shift assay (EMSA), respectively. NF-κB decoy molecules were introduced into T2DM adipocytes, and their effects on all these molecular events evaluated.
Results: Compared with cells from non-diabetic subjects, adipocytes from T2DM patients showed signs of insulin resistance, with significantly reduced IRS-1 tyrosine and AKT (Ser 473) phosphorylation levels in response to insulin stimulation. At the same time, T2DM cells displayed elevated levels of IL-6 and MCP-1, and NF-κB activity. Introduction of NF-κB decoy molecules significantly inhibited both IL-6 secretion and NF-κB activity, while enhancing insulin-stimulated IRS-1 tyrosine and AKT (Ser473) phosphorylation in T2DM adipocytes.
Conclusion: Abdominal subcutaneous fat cells from T2DM patients display signs of insulin resistance and microinflammatory status. NF-κB decoy molecules inhibited NF-κB overactivation and also partly reversed insulin resistance. These results provide evidence of a link between inflammation and insulin resistance in T2DM cells, suggesting a potential contribution of inflammation to the mechanism of insulin resistance.
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