高脂诱导胰岛素抵抗ApoE基因敲除小鼠糖脂代谢的变化

目的建立高脂诱导ApoE基因敲除（ApoE^-/-）小鼠胰岛素抵抗（IR）模型，并探讨其糖脂代谢的变化。方法高脂喂养ApoE叫小鼠16周建立IR模型，采用3-^3H葡萄糖为示踪剂的扩展高胰岛素钳夹技术评价其胰岛素敏感性和糖脂代谢变化。结果普通饲料喂养ApoE^-/-小鼠（NF组）血浆FFA、TC、TG、LDL-C、HDL-C和Ins明显高于C57BL／6J小鼠对照（NC）组（P〈0．01和P〈0．05），而高脂喂养ApoE叫小鼠（HF组）上述指标又明显高于NF组（P均〈0．01），并且FBG也明显高于NF和NC组（P均〈0．01）。钳夹稳态时，HF组Ins明显高于NF和NC组（P均〈0．01），FFA、TC、TG虽被抑制，但仍明显高于NF和NC组（P均〈0．01）；HF组葡萄糖输注率明显低于NF和NC组（P均〈0．01）。在钳夹结束时，HF组葡萄糖清除率明显低于NF和NC组（P均〈0．01），而肝糖输出率则明显高于NF和NC组（P均〈0．01），仅被抑制51％。结论ApoE^-/-小鼠存在糖脂代谢紊乱和IR的遗传特征，长期高脂饲养后更为明显。

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 ApoE^-/- mice with IR induced by high-fat diet. Methods An IR model was established by high-fat diet for 16 weeks in ApoE^- /- mice. 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 （Ins）, free fatty acids （FFA）, TC, TG, LDL-C and HDL-C were significantly elevated in normal-chow fed ApoE^-/- mice （NF group） compared with C57BL/ 6J mice （NC group）（P〈0. 01-0. 05）. In high-fat fed ApoE^-/- mice （HF group）, Ins, FFA, TC, TG, LDL-C and HDL-C were significantly higher than the 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, plasma insulin was significantly higher in the HF group than NF and NC groups （both P〈0.01）. Although FFA, TC and TG were suppressed in all group, they were still higher in HF group than in NF and NC groups （both P〈0.01）. During steady state the glucose infusion rate （GIR） in HF group was significantly decreased as compared with NF and NC group （30. 2±3.1 vs 44. 6±3. 0 and 54. 2 ±2.2 mg · kg^-1· min^-1, P〈0.01）. In the end of insulin clamp, glucose disappearance rate （GRd） was significantly lower in HF group than in NF and NC groups （38. 2±0. 8 vs 48. 0±0. 9 and 55.7±2.0 mg · kg^-1 · min^-1 , both P〈0. 01）, and HGP was significantly higher in the HF group than in NF and NC groups （8.0±5. 5 vs 4. 3 ±2. 3 and 1.2±0. 8mg · kg^-1 · min^-1 , both P〈0. 01）. Conclusions There is an abnormality of glucose-lipid metabolism and insulin resistance in ApoE^-/- mice,especially fed by high-fat.