The Changes Of Glucose-Lipid Metabolism In ApoE^-/- Mice With High-Fat Induced Insulin Resistance

Objective: To establish an insulin resistance (IR) model and investigate the changes of glucose-lipid metabolism in high-fat fed ApoE-/- mice.Methods: Healthy male ApoE-/- mice, eight-week-old, were randomly divided into normal-chow diet fed group (NF group, n=10) and high-fat diet fed group (HF group, n=10) and fed with corresponding food for 16 weeks. In addition , C57BL/6J mice were set as control group(NC group, n=10). The insulin sensitivity and glucose-lipid metabolism in awake mice were evaluated by hyperinsulinemic-euglycemic clamp technique combined with 3- [3H] glucose as a tracer.Results: Plasma insulin (PIns), free fatty acids (FFA), total cholesterol (TC), triglyeride (TG), low density lipoprotein (LDL-C) and high density lipoprotein(HDL-C) were significantly elevated in normal-chow diet fed ApoE-/- mice (NF group) compared with and C57BL/6J mice (NC group, P<0.01 and P<0.05) . In high-fat diet fed ApoE-/- mice (HF group), PIns, FFA, TC, TG, LDL-C and HDL-C were significantly higher than NF group (all P<0.01). Fasting blood glucose (FBG) was also significantly elevated in HF group compared with NF and NC groups ( both P<0.01). During the steady-state of clamp, PIns was significantly higher in NF group than NC group (P<0.01),and PIns was also significantly higher in HF group than NF group (P<0.01). Although FFA, TC and TG were suppressed in all groups, they were still higher in NF group than NC group ( both P<0.01),and also higher in HF group than NF group ( both P<0.01). During steady - state glucose infusion rate (GIR) in NF group was significantly decreased compared with NC group (44.6±3.0 vs. 54.2±2.2 mg·kg-1·min-1,P<0.01),and also GIR in HF group was significantly decreased compared with NF group(30.2±3.1 vs. 44.6±3.0 mg·kg-1·min-1,P<0.01). In the end of insulin clamp, glucose disappearance rate (GRd) was significantly lower in NF group than NC group (48.0±0.9 vs. 55.7±2.0 mg·kg-1·min-1, P<0.01), and also significantly lower in HF group than NF group (38.2±0.8 vs. 48.0±0.9 mg·kg-1·min-1, P<0.01). Hepatic glucose production (HGP) in NF group was significantly higher than NC group(4.3±2.3 vs. 1.2±0.8 mg·kg-1·min-1, P<0.01), and also significantly higher in HF group than NF group(8.0±5.5 vs. 4.3±2.3 mg·kg-1·min-1, P<0.01), suppressed by 51 %.Conclusion: There are an abnormality of glucose-lipid metabolism and insulin resistance in ApoE-/- mice,especially fed by high-fat.