| Objective:To investgate the effects of Liraglutide on insulin sensetivity and glucose-lipid metabolism by RNAi-mediated adiponectin gene inhibition in ApoE-/-mice.Methods:Male ApoE-/- mice were given an intraperitoneal injection of Liraglutide (HEL group, 0.1mg/kg; HEM group,0.5mg/kg; HEH group, 1mg/kg) and saline (HE group) tiwce daily for 8 weeks. The intravenous glucose tolerance test (IVGTT) was performed to evaluate the dose-effective relationship of Liraglutide. HEH group was administered by adiponectin shRNA adenovirus, and a hyperinsulinemic-euglycemic clamp technique combined with 3-[3H] glucose as a tracer was performed for evaluating glucose-lipid metabolism and insulin sensitivity.Results:In IVGTT, blood glucose in HEH group was significantly lower than other groups at 5,15,30 min after glucose-challenge, (all P< 0.01), and plasm insulin levels were significantly increased at 5 and 15 min (both P<0.01). In ApoE-/- mice with Liraglutide and adiponectin shRNA adenovirus treatment (HEA group), Fasting blood glucose(FBG), bodyweight, Free fatty acids (FFA), TC, TG, fasting plasma insulins (Pins) and LDL-C fasting plasma insulins (PIns) were significantly lower than the other groups (P<0.01and P<0.05). However, HDL-C showed a significant elevation, compared HEA with ADI group (P<0.05).During clamp, plasma insulin in ApoE-/-mice with shRNA adenovirus treatment (ADI group) was significantly higher than that in HEA group (P<0.01). Although FFA, TC and TG were suppressed in all groups, they were higher in ADI group than HEA group (P<0.05). Glucose infusion rate (GIR) in HEA group were significantly higher than ADI group (P<0.01). In the end of clamp, glucose disappearance rate (GRd) was significantly lower, and HGP significantly higher in ADI group than HEA group (P<0.01).Conclusion Liraglutide treatment improved glucose-lipid metabolism and insulin resistance in high-fat fed ApoE-/-mice with RNAi-mediated adiponectin gene inhibition. |
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