Adiponectin decreases insulin receptor substrate-1 phosphorylation in the liver of OLETF rats possibly through nuclear factor-κB signaling pathway / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of adiponectin (APN) on the insulin pathway in the liver of OLETF rats and explore its molecular mechanism.</p><p><b>METHODS</b>Twenty male OLETF rats and 10 male LETO rats were sacrificed at 8 and 32 weeks of age to examine the fasting blood glucose, serum insulin, adiponectin and blood lipid profiles. The APN, phosphotyrosine of insulin receptor substrate-1 (IRS-1), IKKβ and nuclear-κB (NF-κB) in the liver tissue were determined using ELISA, Western blotting or immunohistochemistry.</p><p><b>RESULTS</b>The plasma adiponectin level in OLETF rats was significantly lower than that of LETO rats since 8 weeks of age (P<0.01). At 32 weeks of age, the blood lipid levels of OLETF rats increased significantly (P<0.05) with inverse correlations to plasma adiponectin (P<0.01). The liver APN, py-IRS-1, IKKβ and NF-κB levels in OLETF rats differed significantly from those of LETO rats at both 8 and 32 weeks. At 32 weeks of age, the APN level of both rats were correlated to the levels of NF-κB and py-IRS-1 (P<0.01).</p><p><b>CONCLUSION</b>APN may decrease tyrosine phosphorylation of IRS-1 via the IKK/NFκB pathway and inhibit insulin signaling pathway in the liver, which contributes to hyperlipidemia, hyperglycemia and development of type 2 diabetes.</p>