Abstract: Objective: To observe the regulatory effects of sericin on the insulin receptor(IR), insulin receptor substrate-1(IRS-1), phosphatidylinositol-3-kinase(PI3K) and protein kinase B(Akt) in the insulin PI3K/Akt signaling pathway in the rats of type 2 diabetes mellitus,and to discuss the mechanism of sericin in lowering the blood glucose. Methods: Thirty-six SPF male SD rats were randomly divided into normal group, model group and experimental group; there were 12 rats in each group.The rats in model group and experimental group were given with high-fat, high-sugar feeding and intraperitoneal injection of streptozotocin (STZ) of 35 mg·kg^-1·d^-1 for 2 d to establish the type 2 diabetic rat models, and the standard for successfully establishing model was the fasting blood glucose ≥ 11.1 mmol·L^-1 after injecting STZ for 72 h. After successfully establishing the diabetes models,the rats in experimental group were given sericin(2.4 mg·kg^-1·d^-1) by gavage, and the rats in normal group and model group were lavaged with the equal volume normal saline; lasted for 35 d. The glucose oxidase method was used to detect the fasting blood glucose of the rats in various groups.Immunohistochemical staining and Western blotting methods were used to detect the expressions of IR, IRS-1, PI3K and Akt proteins in liver tissue of the rats in various groups and periodic acid-schiff staining was used to determine the contents of liver glycogen of the rats in various groups. Results: The blood glucose level of the rats in model group was significantly higher than that in normal group(P<0.05), and the blood glucose level of the rats in experimental group was obviously lower than that in model group(P<0.05).The expressions of IR, IRS-1,PI3K and Akt proteins were tan granules located in the rat liver slices in normal and experimental groups,and some of positive proteins were diffuse;the expression amounts of IR,IRS-1,PI3K and Akt proteins in liver tissue of the rats in model group were significantly decreased,and they were tan granules;the IR, IRS-1 and Akt proteins were mainly located in the membrane and cytoplasm of hepatocytes, while the PI3K protein was mainly located in the cytoplasm of hepatocytes.The staining of liver glycogen of the rats in various groups was red or purple granules; the staining of liver glycogen of the rats in model group was relative light,and the area was small. Compared with normal group, the expression levels of IR,IRS-1,PI3K and Akt proteins and the content of liver glycogen in liver tissue of the rats in model group were decreased significantly(P<0.05);compared with model group, the expression levels of IR,IRS-1,PI3K,and Akt proteins and the content of liver glycogen in liver tissue of the rats in experimental group were increased significantly(P<0.05). Conclusion: Sericin can enhance the transduction effect of liver insulin PI3K/Akt signaling pathway by up-regulating the expressions of IR, IRS-1, PI3K and Akt in the liver tissue of the rats of type 2 diabetes mellitus, thus reduce the blood glucose level.

Key words: sericin, type 2 diabetes mellitus, liver, insulin, PI3K/Akt signaling pathway