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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~(-/-)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~(-/-)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。
Objective To establish a model of insulin resistance (IR) induced by high fat-induced ApoE knockout (ApoE ~ (-) -) in mice and to explore the changes of its glycolipid metabolism. Methods The IR model was established in high fat diet ApoE ~ (- / -) mice for 16 weeks. The insulin sensitivity and glucose and lipid metabolism were evaluated by extended insulin hypermyocardial clamp with 3- ~ 3H glucose as tracer. Results The levels of plasma FFA, TC, TG, LDL-C, HDL-C and Ins in normal diet fed ApoE ~ (- / -) mice were significantly higher than those in C57BL / 6J mice (P <0.01), and FBG was also significantly higher than that in NF and NC groups (P <0.05), while the high fat diet ApoE ~ (- / -) mice All <0.01). In the steady-state clamp, the Ins of HF group was significantly higher than that of NF and NC groups (P <0.01), while the levels of FFA, TC and TG were significantly lower than those of NF and NC groups (P <0.01) The glucose infusion rate was significantly lower than NF and NC groups (P <0.01). At the end of the clamp, the glucose clearance rate in HF group was significantly lower than that in NF and NC groups (P <0.01), while the hepatic glucose output rate was significantly higher than that in NF and NC groups (P <0.01) . Conclusion _ApoE ~ (- / -) mice have glucose and lipid metabolism disorders and genetic characteristics of IR, long-term high-fat diet is more obvious.