Mechanism of Rh-SAA mediating 3T3-L1 adipocytes insulin resistance

Wang, Yanping ; Cao, Hong ; Hua, WenJin Hua ; Dong, QiaoJing ; Zhang, Liang ; Cao, Min ; Xie, Yu ; Xue, Jun Xue


Insulin resistance is a manifestation of both diabetes mellitus and obesity. Insulin signaling and its impairment in obesity and type 2 diabetes continue to excite researchers. Permanent increase in acute-phase serum amyloid A (A-SAA) level has been observed and correlated to both obesity and insulin resistance in humans. In this study, we explored the mechanism of recombinant serum amyloid A (Rh-SAA) mediating insulin resistance and JNK activation of 3T3-L1 adipocytes. We could observe the effect of Rh-SAA on insulin sensitivity of 3T3-LI adipocytes under the intervention of JNK inhibitors. We selected three experimental groups viz. (i) NC Group: Adipocytes without Rh-SAA intervention,;(ii) Rh-SAA Group: A dipocytes with 20μg/mL Rh-SAA intervention; and (iii) JNK Inhibitor Group: Adipocytes pretreated with 50 μmol/L JNK inhibitor SP600125 12 h before 20 μg/mL Rh-SAA intervention. All the three groups were incubated for 48 h, the glucose transport rate of the adipocytes was measured by3H-2-DG, and the level of JNK activation was examined using Western blotting. Compared with the NC group, glucose uptake in the adipocytes treated with 20μg/mL Rh-SAA for 48 h decreased by 26% (P <0.01). The glucose uptake increased by 15% (P <0.05) in the JNK Inhibitor group. Western blotting showed that the expression levels of p-JNK in the NC group and Rh-SAA group and JNK inhibitor group were 100, 166 and 107%, respectively. Compared with NC group, the phosphorylation of JNK increased by 66% (P <0.01), but JNK inhibitor group showed no significant difference between Rh-SAA group (P <0.01) and NC group (P <0.05). Results suggested that intervening activity of JNK is expected to be an effective treatment for insulin resistance related diseases.


Diabetes mellitus; Jun N-terminal kinase (JNK) pathway; Obesity, Recombinant SSA; Serum amyloid A proteins

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