Involvement of the PI3K/Akt pathway in the hypoglycemic effects of sea cucumber Apostichopus japonicas in diabetic rats

The present study was designed to evaluate the effect of sea cucumber Apostichopus japonicus treatment on fasting plasma glucose, glucose tolerance, serum insulin level and insulin signaling pathway in streptozotocin(STZ)-induced diabetic rats. The diabetic rat model was generated by injection intraperitoneally with STZ (60 mg/kg). The diabetic rats were divided into two groups: the model control group and sea cucumber group. Rats in sea cucumber group were administered orally with A. japonicus(800 mg/kg). The other rats were given with 0.9% NaCl solution as placebo. All agents were administered once a day for 35 days. Changes in blood glucose level, oral glucose tolerance and insulin secretion index were routinely evaluated. The expressions of phosphatidylinositol 3 kinase(PI3K), protein kinase B(PKB) and glucose transporter 4(GLUT4) in skeletal muscle and adipose tissues were determined with reverse transcription PCR (RT-PCR) or Western blot. The results show that A. japonicas can reduce the fasting plasma glucose, improve glucose tolerance and serum insulin contents in diabetic rats significantly. RT-PCR and Western blotting analysis revealed that A. japonicas treatment caused a significant increase in the expression levels of PI3K, PKB and Glut4 mRNA in both skeletal muscle and adipose tissues, and GLUT4 protein in adipose tissues, whereas there was no significant change in the expression of GLUT4 protein in skeletal muscle tissue compared with the diabetic control rats. These results indicate that A. japonicas is beneficial for improving hyperglycemia by enhancing part of the signal transduction pathway of PI3K/PKB/Glut4 in insulin sensitive skeletal muscle and adipose tissues.