日本刺参降血糖及对胰岛素信号通路的影响

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

以腹腔注射链脲佐菌素建立糖尿病大鼠模型,用日本刺参(Apostichopus japonicas)灌胃糖尿病大鼠35 d,观察其对大鼠空腹血糖、葡萄糖耐量和血清胰岛素的影响,并对其作用机制进行探讨.采用逆转录聚合酶链式反应(reverse transcription polymerase chain reaction,RT-PCR)技术检测糖尿病大鼠骨骼肌和脂肪组织中磷脂酰肌醇-3-激酶(phosphatidylinositol 3 kinase,PI3K)、蛋白激酶B(protein kinase B,PKB)和葡萄糖转运蛋白4(glucose transporter,GLUT4)等基因mRNA表达水平,Western blot方法检测GLUT4蛋白表达水平.结果显示,日本刺参能显著降低糖尿病大鼠空腹血糖含量,提高口服葡萄糖耐量和血清胰岛素含量;提高骨骼肌和脂肪组织中PI3K、PKB和Glut4 mRNA表达量,促进脂肪组织中GLUT4蛋白表达.日本刺参对糖尿病大鼠脂肪组织PKB mRNA表达和骨骼肌GLUT4蛋白表达无显著性影响.提示日本刺参具有较好的降血糖作用,其作用机制与部分上调胰岛素介导的PI3K/PKB/Glut4信号转导通路有关.

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.