The Mechanisms Of Blood Glucose-lowering Of Agaricus Blazei Murill Polysaccharide

[Objective] To investigate the effects of Agaricus blazei Murill polysaccharide (ABPS) on serum glucose, insulin concentration, serum protein, TC, TG, hepatic glycogen content and renal histopathological changes in alloxan-induced diabetic mice, and explore the effects on the expression of GLUT4、PI3K、Akt1and Akt2in the muscle and lipid of diabetic mice. The present study is undertaken to investigate the possible action mode of ABPS and probe into the mechanisms for controlling diabetic mellitus.[Methods] In the test,48healthy (30±2) g male mice were randomly divided into six groups, and named as normal control (NC) group, diabetic model group, Agaricus blazei Murill polysaccharide low dose group, middle dose group, high dose group and Acarbose treatment group, respectively. Mice in the NC group and model group were given0.9%normal saline. Mice in the low dose group, middle dose group, high dose group were administered orally with different doses (50,100and200mg/kg body weight) of ABPS. Mice in the treatment group were given Acarbose (200mg/kg body weight) everyday. After7weeks of administration, the liver, kidney, spleen were collected and the viscera index were calculated. And serum glucose, insulin concentration, serum protein, TC, TG, hepatic glycogen content and renal histopathological changes were also detected. In addition, expression levels of Glut4, PI3K, Aktl and Akt2were studied by real-time RT-PCR.[Results](1) The weight of mice in NC group gradually increased in the study. The weight of mice in the model group decreased firstly and increased subsequently. There was significant difference on weight increase between the model group and NC group (P<0.01). The weight increased least in the mice of model group, and it was the largest in mice of high dose group and treatment group. Compared with the NC group, liver and kidney index increased and spleen index decreased in mice of the model group, and there were significant differences (P<0.05or P<0.01).(2) Compared with the NC group, the content of serum glucose in mice of model group significantly increased (P<0.01); insulin concentration in model group significantly decreased (P<0.01); the content of serum protein in model group significantly increased (P<0.05); TC and TG content in model group significantly increased (P<0.01); hepatic glycogen content in model group significantly increased (P<0.01). Compared with the model group, serum glucose and TG in ABPS groups significantly decreased (P<0.05or P<0.01), serum protein, TC in middle low group and high dose group significantly decreased(P<0.05or P <0.01),insulin concentrations, hepatic glycogen content significantly increased (P<0.05or P<0.01).(3) Compared with the NC group, we observed that glomerulus hypertrophy, glomerulus extracellular matrix accumulating, basement membrane thickening and glomerulosclerosis in mice of model group. Compared with the model group, it showed that glomerular basement membrane thinning, mesangial cells mild hyperplasia, minor glomerular capillary blood clot in ABPS groups. It also displayed that glomerular volume slightly swollen, mild hyperplasia of mesangial cells, no obvious broadening mesangial area, and glomerular basement membrane structure basic returned to normal in mice of treatment group.(4)①Compared with the NC group, the expression of GLUT4、PI3K、Akt1and Akt2in the muscle of model group significantly decreased (P<0.05or P<0.01). Compared with the Model group, the expression of GLUT4、PI3K、Akt1and Akt2in the muscle of ABPS groups increased, and GLUT4in ABPS groups, PI3K in high dose group, Akt1and Akt2in middle, high dose groups significantly increased(P<0.05or P<0.01). Compared with the model group, the expression of GLUT4、PI3K、Akt1and Akt2in the muscle of mice in the treatment group significantly increased (P<0.01).②Compared with the NC group, the expression of GLUT4、PI3K、Akt1and Akt2in the lipid of model group significantly decreased (P<0.05or P<0.01). Compared with the model group, the expression of GLUT4、PI3K、Akt1and Akt2in the lipid of ABPS groups increased, and GLUT4, Akt1in ABPS groups, PI3K in high dose group, Akt2in middle, high low groups significantly increased (P<0.05or P<0.01). Compared with the model group, the expression of GLUT4、PI3K、Akt1and Akt2in the lipid of treatment group significantly increased (P<0.01).[Conclusion] In conclusion, the results of the present study demonstrate that ABPS exerts anti-hyperglycemic effects. It could control the blood glucose levels and increase the levels of insulin in diabetic mice. Meanwhile, it could increase the mRNA expression of GLUT4, PI3K, Akt1and Akt2. The findings signify that ABPS has the potential as a promising source of natural hyperglycemic agent.