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.

中文翻译：

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Rh-SAA介导3T3-L1脂肪细胞胰岛素抵抗的机制

胰岛素抵抗是糖尿病和肥胖症的表现。胰岛素信号及其在肥胖症和2型糖尿病中的损害继续引起研究人员的兴趣。已观察到人类急性期血清淀粉样蛋白A（A-SAA）水平永久升高，并与肥胖和胰岛素抵抗相关。在这项研究中，我们探讨了重组血清淀粉样蛋白A（Rh-SAA）介导3T3-L1脂肪细胞的胰岛素抵抗和JNK激活的机制。在JNK抑制剂的干预下，我们可以观察到Rh-SAA对3T3-LI脂肪细胞胰岛素敏感性的影响。我们选择了三个实验组。（i）NC组：未经Rh-SAA干预的脂肪细胞;（ii）Rh-SAA组：经20μg/ mL Rh-SAA干预的A细胞; （iii）JNK抑制剂组：在20μg/ mL Rh-SAA干预之前12 h，用50μmol/ L JNK抑制剂SP600125预处理的脂肪细胞。将这三组均孵育48小时，通过以下方法测量脂肪细胞的葡萄糖转运速率：³ H-2-DG，并使用蛋白质印迹法检查JNK活化水平。与NC组相比，用20μg/ mL Rh-SAA处理48小时的脂肪细胞的葡萄糖摄取降低了26％（P <0.01）。在JNK抑制剂组中，葡萄糖摄取增加了15％（P <0.05）。Western blotting结果显示，NC组，Rh-SAA组和JNK抑制剂组的p-JNK表达水平分别为100、166和107％。与NC组相比，JNK的磷酸化增加了66％（P <0.01），但JNK抑制剂组显示出的Rh-SAA组之间无显著差异（P和NC组<0.01）（P<0.05）。结果表明，干预JNK活性有望成为治疗胰岛素抵抗相关疾病的有效方法。