The Effect Of Chalcones Extracted From Angelica Keiskei On Insulin Resistance Of Type ? Diabetes

ObjectiveTo investigate the effect of chalcones extracted from Angelica keiskeion(AC)on insulin resistance of skeletal muscle with type 2 diabetes in vivo and vitro.MethodsIn vitro study:Differentiated L6 cell line with insulin resistance induced by high insulin was incubated with Angelica keiskei chalcones at the concentrations of 20?mol/L,10?mol/L and 5 ?mol/L for 24 h.The contents of glucose in the supernatant were determined by using glucose oxidase method.The mRNA expression of PI3K and Akt was evaluated by reverse transcription polymerase chain reaction(RT-PCR).The protein of Akt and GLUT4 was measured by western blot.In vivo study:Diabetic rats were induced by high-fat feeding and streptozotocin with intraperitoeal injection.The rats were divided into 3 groups randomly with 10 rats in each group as diabetic control group,high-dose AC group and low-dose AC group fed with high-fat diet.AC with 0,35 and 10 mg/kg BW per day were given to diabetic control,high-dose AC and low-dose AC groups,respectively.Another 10 normal rats were fed with regular diet as the normal control group.After 4 weeks,blood glucose levels were measured by glucose oxidase method.Serum insulin levels were determined by radioimmunoassay.The contents of triglyceride(TG)in skeletal muscle were measured by automatic biochemical analyzer.The mRNA expression of AMPK and ACC were determined by reverse transcription polymerase chain reaction(RT-PCR).The phosphorylation levels of ACC were analyzed by western blot.ResultsIn vitro study:Compared with the normal control,the glucose content in supernatant of L6 cells with insulin resistance was increased while the PI3K mRNA,Akt mRNA and the protein of Akt and GLUT4 were decreased.The glucose content in supernatant of L6 cells incubated with 20 ?mol/L and 10?mol/L were decreased while the mRNA expression of PI3K and Akt and the protein expression of Akt and GLUT4 were increased comparing with the insulin resistance control.All the difference was significantly different(P<0.05).In vivo study:Blood sugar,serum insulin and TG in skeletal muscle of rats fed with high dose AC were all significantly lower than those of the diabetic control group(P<0.05).Their expression of AMPK mRNA and phosphorylated ACC were both significantly higher than those of the diabetic control group(P<0.05).And ACC mRNA expression of high-dose AC group were significantly decreased comparing with the diabetic control group(P<0.05).ConclusionAngelica keiskei chalcones may improve the insulin resistance of type 2 diabetes through activating the PI3K-Akt-GLUT4 and AMPK-ACC signaling.