Abstract: 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.

Key words: type 2 diabetes mellitus, fish oil, glucose metabolism, insulin resistance, PI3K/Akt signaling pathway