JAZF1基因过表达对小鼠糖脂代谢及胰岛素敏感性的影响

The effects of JAZF1gene over-expression on glucose and lipid metabolism and insulin sensitivity in C57BL/6J mice

目的探讨JAZF1基因过表达对高脂饮食诱导的IR小鼠糖脂代谢及IS的影响。方法 43只雄性C57BL/6J小鼠,随机分为普食对照组(NF,n=10)和高脂组(n=26)。高脂组喂养12周后,再随机分为高脂+生理盐水组(HF,n=10)、高脂+空载组(GF,n=6)和高脂+JAZF1质粒组(JAZF1,n=10)。质粒于钳夹前48h经颈静脉注射。扩展胰岛素钳夹技术评价IS。结果肝组织JAZF1mRNA及蛋白表达HF组和GF组较NF组降低,而JAZF1组高于HF、GF组(P均<0.05)。JAZF1组FBG、TC、FIns和肝脏TC水平较HF、GF组降低(P<0.05)。钳夹稳态时,JAZF1组葡萄糖输注率(GIR)(26.39±1.65)mg/(kg·min)高于HF组(21.37±0.49)mg/(kg·min)和GF组(22.01±0.89)mg/(kg·min)(P<0.05)。钳夹结束时,葡萄糖清除率(GRd)JAZF1组(32.23±2.12)mg/(kg·min)高于HF组(29.66±0.87)mg/(kg·min)和GF(30.13±1.15)mg/(kg·min)组(P均<0.05),而肝糖输出率(HGP)JAZF1组(5.84±0.88)mg/(kg·min)低于HF组(8.29±0.39)mg/(kg·min)和GF组(8.13±0.76)mg/(kg·min)(P均<0.05)。结论高脂诱导的IR小鼠JAZF1基因表达下调,而JAZF1基因过表达可改善高脂诱导的糖脂代谢异常和IR。

Objective To explore the effects of the juxtaposed with another zinc finger gene 1 （JAZF1） over-expression on glucose and lipids metabolism as well as insulin sensitivity in insulin resistant C57BL/6J mice induced by high fat diet （HFD）.Methods Forty-three male C57BL/6J mice were randomly divided into two groups including regular diet group （NFD group,n=10） and high fat diet group （HFD group,n=26）.Twelve weeks later,the HFD rats were randomly divided into 3 groups：HFD fed＋saline group （HF group,n=10）,HFD fed ＋ empty vector group （pIRES2-EGFP,GF group,n=6） and HFD fed ＋ JAZF1 plasmid group （pIRES2-EGFP-JAZF1,JAZF1 group,n=10）.pIRES2-EGFP or pIRES2-EGFP-JAZF1 were injected intravenously 48 hours before clamping.The hyperinsulinemic-euglycemic clamp technique was applied to assess insulin sensitivity.Results JAZF1 mRNA and protein levels in liver were significantly lower in HF and GF groups than in NF group （all P〈 0.05）,and they were significantly increased in JAZF1 group （all P〈0.05）.FBG,TC,FIns and liver TC were significantly lower in JAZF1 group than in HF and GF groups （P〈0.01 or P〈0.05）.During steady-state of clamping,the glucose infusion rate [GIR （26.39 ± 1.65） mg/（kg · min）]and glucose disappearance rate [GRd（32.23±2.12） mg/（kg · min）] were significantly higher in JAZF1 group than in HF [GIR（21.37±0.49） mg/（kg · min）,GRd（29.66±0.87）mg/（kg · min）] and GF [GIR（22.01± 0.89） mg/（kg · min）,GRd （30.13±1.15） mg/（kg · min） groups,P〈0.05 or P〈0.01],and hepatic glucose production （HGP） was significantly lower in JAZF1 group （5.84±0.88）mg/（kg · min） than in HF（8.29±0.39） mg/（kg · min） and GF（8.13±0.76） mg/（kg · min） groups （all P〈0.05）.Conclusion JAZF1 over expression could effectively improve the disorder of glucose and lipid metabolism and insulin resistance.