The Effect And Molecular Mechanisms Of Sangguayin Through The PI3K/Akt Signaling Pathway In Type 2 Diabetes Mellitus Rats

ObjectivesSangguayin(SGY)is an experienced agent in traditional Chinese medicine,and consists of Folium Mori,Fructus Momordicae Charantiae,Radix Puerariae Lobatae and Rhizoma Dioscorea.The hypoglycemic effects and mechanisms of SGY extracts on insulin resistance through the PI3K/Akt signaling pathway in T2 DM rats were investigated.MethodsThe T2 DM rats were induced by a high-fat diet and streptozotocin.The rats were separated at random into the following four groups(n= 8/group):control group(nondiabetic rats treated with saline),T2 DM group(T2DM rats treated with saline),metformin group(T2DM rats treated with metformin),and SGY group(T2DM rats treated with SGY extract).Saline at a dosage of3ml/kg b.w.,metformin at a dosage of 150mg/kg b.w.,and SGY at a dose of1240mg/kg b.w.were dissolved in saline and administered orally by gavage daily for 42 successive days.Body weight,water,and food intake were quantified every two weeks.35 days later,oral glucose tolerance tests(OGTT)were conducted.And 42 days later,fasting blood glucose(FBG)and homeostatic model assessments of insulin resistance(HOMA-IR)were quantified.Blood insulin,triglycerides,total cholesterol,LDL,HDL,glycogencontent,glycosylated hemoglobin(GHb),SOD,MDA,CAT,and GSH-Px were measured.Paraffin wax slices were used to collect pathological sections of the pancreas,liver and kidney.And the pathological changes of the pancreas,liver and kidney were evaluated by hematoxylin/eosin insulin staining.Protein expression of the insulin signaling pathway in the liver was quantified.PI3K/Akt signaling pathway-related genes and proteins in the liver were tested by real-time PCR(RT-PCR)and western blot analysis,respectively.ResultsIndicators of glucose metabolism: SGY treatment was observed to reduce FBG、FINS、HOMA-IR、OGTT compared with the T2 DM group(P< 0.05 or P< 0.01).Biochemical parameters: SGY treatment was observed to reduce TC,TG,LDL and GHb,and increase hepatic glycogen and HDL in T2 DM rats(P<0.05 or P< 0.01).Pathological changes: SGY treatment showed significantly ameliorated pathological changes and reduced inflammation in the pancreas,liver and kidney.Indicators of oxidative stress: SGY treatment was observed to reduce MDA,and increase SOD,CAT and GSH-Px in T2 DM rats(P< 0.05 or P<0.01).PI3K/Akt signaling pathway: SGY treatment was also observed to up-regulate gene and protein expressions of InsR,IRS-2,PI3 K,Akt,and GLUT-4 in the livers of T2 DM treated rats(P< 0.05).Conclusions1.SGY had hypoglycemic properties,improved glucose metabolism,and might alleviate insulin resistance in T2 DM rats.2.SGY significantly regulated the levels of blood lipid and improvedlipid metabolism in T2 DM rats.3.SGY reduced the damage of pancreatic β-beta cells and the pathological changes in liver,pancreas and kidney,and played a protective role in pancreas,liver and kidney tissue in type 2 T2 DM rats.4.SGY improved the antioxidant ability and ameliorated the state of oxidative stress in type 2 T2 DM rats.5.It is reasonable to suggest that SGY may improve IR through the PI3K/Akt pathway.