Clinical study on the relationship between the activation of the IKK-IκB-NFκB pathway and insulin resistance / 中华内分泌代谢杂志

ABSTRACT

Objective To explore the difference involved in the activation of inflammation pathway and the plasma level of inflammatory factors in the subjects with different sorts of insulin sensitivity. Methods The study was carried out in 38 women, consisting of obesity (n = 22 ) and control (n = 16 ) groups according to body mass index. The insulin sensitivity was assessed by homeostasis model assessment of insulin resistance (HOMAIR). Plasma concentrations of interleukin-6 (II-6) and IL-1β were determined by enzyme immunoassay. Western blot analysis was used to examine total protein expression and phosphorylation levels of IκB kinase (IKK) ,inhibitor of nuclear factor-κB ( IκB ) in peripheral blood leukcocytes. Electrophoretic mobility shift assay (EMSA)was used to detect the binding activity of NFκB. Results The levels of fasting plasma insulin[62.2 ( 20.0-127. 0) pmol/L vs 19. 15 ( 14. 2-47. 8 ) pmol/L, P<0. 01], HOMA-IR[2. 32 ( 0. 76-5.49 ) vs 0.70(0.53-1.7),P<0.0l], HbA1 C[(5.42±0. 45 ) % vs ( 5.08 ±0. 38) %, P<0. 05], triglyceride[( 1.75 ±0. 68 vs 1.22 ±0. 58 )mmol/L, P<0. 05], plasma IL-6[3. 15 (0. 03-22. 2) pg/ml vs 1.26 (0. 74-6.06 ) pg/ml, P<0. 01], and IL-1 β[6. 53 ( 0. 84-36 ) pg/ml vs 3. 16( 1.48-8. 86 ) pg/ml, P<0. 01]in obesity group were significantly higher than those in control group. Compared with control group, the levels of IKKo, IKKβ expression and IκBα serine phosphorylation in obesity group were markedly increased, while the expression of IκBα was significantly reduced. Accompanied with the degradation of IκBα protein, the binding activity of NFκB in obesity group was significantly increased. Conclusions The plasma levels of IL-6 and IL-1β were significantly raised in obesity group. The activation of IKK-IκB-NFκB pathway is closely associated with the genesis and development of insulin resistance in obese subjects.