Molecular Mechanism of Parthenolide Improving Insulin Resistance Induced by Insulin / 医药导报

ABSTRACT

Objective To investigate the reversal effect and molecular mechanisms of NF-κB inhibitor parthenolide (PTL) on insulin resistance ( IR). Methods HepG2 cells were treated with insulin at different concentrations and time points, the glucose consumption of HepG2 cells was measured via glucose oxidase method to determine the best concentrations and time for establishing insulin-induced insulin resistance on HepG2 cells. After modeling, different concentrations of PTL were added in cells for 24 h for determining cell activity and glucose-consumption. Q-PCR was used to detect the expression of NF-κB and IκBα mRNA in cells, and western blot was used to detect the expression of protein IκBα. Results The best reaction time and concentration for insulin inducing resistance of HepG2 cells were 24 h and at 10 μg·mL-1 . The optimum acting dose of PTL was 20 μmol·L-1 . NF-κB activity was significantly reduced (P<0. 05), IκBα degradation was significantly inhibited (P<0. 05) compared to HepG2 cells with insulin resistance upon intervention on insulin resistance HepG2 cells by PTL. Conclusion PTL can inhibit IκBα degradation and disassociation of it from NF-κB, which in turn improves insulin resistance, providing theo-retical basis for preventing and treating diabetes with PTL.