鱼油对KKAy糖尿病小鼠糖代谢及PI3K/Akt信号通路的影响

摘要

目的:探讨鱼油对KKAy糖尿病小鼠糖代谢及磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)信号通路的影响.方法:40?只KKAy小鼠,分为模型组和鱼油低、中、高剂量组,每组10?只.另设10?只C57BL/6小鼠为正常对照组.灌胃12?周后,测定血糖、胰岛素、脂联素、瘦素及PI3K/Akt信号通路中相关基因的表达水平.结果:与模型组相比,鱼油低剂量组血糖水平极显著降低(P＜0.01),鱼油低、中剂量组胰岛素水平显著提高(P＜0.05),鱼油各剂量组的脂联素水平显著提高(P＜0.05).此外,鱼油各剂量组可上调胰岛素受体底物-1、 PI3K 、 Akt 、葡萄糖转运蛋白-4基因的表达,其中低剂量鱼油对Akt和葡萄糖转运蛋白-4基因的调控效果更显著.结论:低剂量鱼油可能通过调节PI3K/Akt信号通路改善糖代谢.%Objective: To investigate the effect of fish oil on glucose metabolism and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in diabetic KKAy mice. Methods: Forty KKAy mice were randomly assigned into four groups: diabetic model group, low-dose fish oil group, medium-dose fish oil group and high-dose fish oil group. Ten male C57BL/6 mice served as a non-diabetic control group. Blood and tissue samples were collected after 12 weeks of treatment. Blood glucose, serum insulin, adiponectin, leptin, and the mRNA expressions of insulin receptor substrate-1 ( IRS-1 ), PI3K, Akt and glucose transporter-4 (GLUT-4) were detected. Results: Compared with the model group, fasting blood glucose was reduced significantly in the low-dose fish oil group (P ＜ 0.01), fasting insulin was increased in both the low and medium-dose groups (P ＜ 0.05), and adiponectin level was significantly increased in all the treatment groups (P ＜ 0.05). In addition, fish oil at all doses up-regulated the mRNA expression of IRS-1 , PI3K , Akt and GLUT-4 and at low dose had more significant effect on the mRNA expression of Akt and GLUT-4. Conclusion: Fish oil at low dose may improve glucose metabolism by regulating the PI3K/Akt signaling pathway.