Effects Of Piperine On The Activities Of AMPK And GLUT4 In Insulin Resistance Rats

objective:To explore the effects and mechanism of PIP to ameliorate IR, the effects of Piperine(PIP) on AMPKα and GLUT4 were observed,which are the critical factors of AMPK signaling pathway of IR rat model induced by high-fat diet. Methods:After adapted for 1 week, the 90 healthy male SD rats(180-220g) were randomly divided into 2 groups: Normal control(NC) group(n=15) and high-fat diet group(n=75). The NC group was fed on normal diet for 12 weeks. After fed on high-fat diet for 4 weeks, the high-fat diet group(n=75) was randomly divided into 5 groups: Model control(MC) group, rosiglitazone(ROG) group(3mg/kg) and 3 PIP groups(15mg/kg, 30mg/kg, 60mg/kg). The 5 groups were fed on high-fat diet for 8 weeks. After the 4th week, all the treatment groups were respectively treated with gavage of ROG and PIP according to the designed doses by 0.5ml/100 g for 8 weeks, while NC group and MC groups were treated with gavage of the equal volume of menstruum in the same way. The fasting blood glucose(FBG), fasting insulin(FINS), free fatty acids(FFA), triglyceride(TG), blood pressure(BP) and insulin sensitivity index(ISI) were observed dynamically every 4 weeks and the body weight(BW) were observed dynamically every 2 weeks. The oral glucose tolerance test(OGTT) was observed after treatment with ROG and PIP for 8 weeks. The m RNA levels of AMPKα1, AMPKα2 and GLUT4 in liver and muscle were tested using Real-time PCR. While the protein levels of total AMPKα, p-AMPKα and GLUT4 in liver and muscle were tested by Western blot. HPLC detection the adenosine monophosphate and adenosine triphosphate ratio(AMP/ATP) in liver. Results:1 After feeding on high-fat diet for 12 weeks, the IR rat model was successfully established. Compared with MC group, the levels of FBG, TG, FFA and BP and increased ISI and OGTT of IR rats were reduced.by PIP and ROG2 Compared with MC group, the p-AMPKα/AMPKα ratio in liver and muscle and the AMP/ATP ratio in liver of IR rats were increased by PIP and ROG3 Compared with MC group, the m RNA expression and protein expression of GLUT4 in muscle and the protein expression of GLUT4 in liver of IR rats were increased by PIP and ROG Conclusion:PIP and ROG could regulate the abnormal metabolism of glucose and lipid in ininsulin resistance model rats and showed the function to ameliorate IR. The mechanism of PIP to ameliorate IR is connected with increasing p-AMPK alpha protein expression to activate...