Experimental Study On The Effect Of Xinrunkuxie Recipe On PPAR-? In Insulin Resistant Rats

Objective: To investigate the effect of xinrunkuxie formula(tangyining granules)on the important downstream protein of peroxisome proliferator activated receptor-?(PPAR-?)in insulin resistant rats.Methods: The model of type 2 diabetic Ir Rats was established by intraperitoneal injection of Streptozocin combined with high fat diet,thirty-six rats were randomly divided into normal group,model group,low-dose Tangzhining Granule Group,middle-dose Tangzhining Granule Group,high-dose tangzhining granule group and pioglitazone group.After 6 weeks of drug intervention,the levels of NEFA and ADP in serum of each group were detected by enzyme-linked immunosorbent assay(ELISA),and the genes related to liver insulin resistance were detected by reverse transcription polymerase chain reaction(RT-PCR)The mRNA expression of PEPCK,IRS-2 and GLUT2 was detected by Western blot.The expression of PEPCK,IRS-2 and GLUT2 in liver and GLUT4 in muscle were detected by Western blot.Results:1.After 6 weeks of intraperitoneal injection of Streptozocin combined with high-fat Diet,Fasting Blood Glucose(FBG),triglyceride and Serum Insulin(FINS)in model group were significantly higher than those in normal group,and insulin sensitivity index(ISI)was significantly lower than that in normal group,the differences were statistically significant(P<0.01);2.After 6 weeks of drug intervention,compared with the model group,the serum ADP concentration of rats increased,the NEFA concentration decreased,the difference was statistically significant(P<0.05);the expression level of PEPCK mRNA in liver tissue of rats in each treatment group was significantly down regulated,the expression level of IRS-2 mRNA was significantly up regulated,and the expression level of GLUT2 mRNA was significantly up regulated,The difference was statistically significant(P<0.01 or P<0.05);PEPCK in liver tissue of each group The protein expression of GLUT2 and GLUT4 in the middle,high dose and pioglitazone groups of tangyining granules wassignificantly up-regulated(P<0.05).The difference was statistically significant(P<0.01 or P<0.05).The protein expression of GLUT2 and GLUT4 in the low dose group of tangyining granules was not significantly up-regulated(P>0.05);3.After 6 weeks of drug intervention,compared with pioglitazone group,the ADP concentration of high,medium and low dose group of tangyining granules was lower than that of pioglitazone group,and the NEFA concentration of low dose group of tangyining granules was higher than that of pioglitazone group,the difference was statistically significant(P<0.05),The ADP concentration in high dose group was higher than that in pioglitazone group,and the NEFA concentration in middle and high dose group was higher than that in pioglitazone group,the difference was not statistically significant(P>0.05);The mRNA expressions of PEPCK,IRS-2 and GLUT2 were up-regulated in the middle and low dose group of tangyining granules,down regulated in IRS-2 and GLUT2,and the difference was statistically significant(P<0.05 or P<0.01).The mRNA expressions of PEPCK,IRS-2 and GLUT2 were up regulated in the high dose group of tangyining granules,but the difference was not statistically significant(P>0.05);The protein expression of PEPCK was up-regulated,IRS-2,GLUT2 and GLUT4 were down regulated in the middle and low dose groups of tangyining granules,the difference was statistically significant(P<0.05 or P <0.01),The protein expression of PEPCK and GLUT2 was up-regulated in the high dose group of tangyining granules,but IRS-2 and GLUT4 were down regulated in the high dose group of tangyining granules,the difference was not statistically significant(P>0.05).Conclusion: 1.Insulin resistance was induced by intraperitoneal injection of Streptozocin combined with high-fat Diet at 6 weeks,so the disturbance of Glucose and Lipid metabolism caused by high-fat and high-sugar Diet may be the main cause of insulin resistance in rats;2.Xinrunkuxie recipe can reduce the weight of type 2 diabetic rats with insulin resistance,reduce the FFA in serum,increase the content of adiponectin,regulate the differentiationof adipocytes,and have the effect of reducing lipid;3.The mechanism of xinrunkuxie recipe to improve insulin resistance may be through inhibition Making PEPCK expression,increasing the expression of IRS-2,GLUT2 and GLUT4 protein,promoting the transport and utilization of glucose in peripheral tissues such as muscle and adipose tissue,increasing insulin sensitivity,promoting glycogen synthesis in liver and reducing hepatic gluconeogenesis,so as to reduce blood sugar;4.Different doses of tangyining granules improve insulin resistance in type 2 diabetic rats,and the higher the dose,the higher the pancreas 5.There is no significant difference between the effect of high dose tangyining granule and pioglitazone on insulin sensitivity.The mechanism may be through activating PPAR-? to regulate glucose and lipid metabolism.