外源性胰岛素干预对高脂饮食诱导的糖尿病小鼠肝脏胰岛素信号通路的影响

Effects of exogenous insulin intervention on insulin signaling pathway in the liver of diabetic mice

目的通过基因芯片技术探讨外源性胰岛素干预对糖尿病小鼠肝脏胰岛素信号通路的影响。方法30只5周龄的C57BL/6小鼠随机分为3组:A组为正常饮食组;B组为高脂饮食组;C组为高脂饮食胰岛素干预组。喂养12周后,C组小鼠接受甘精胰岛素0.5IU/d皮下注射。4周后处死小鼠,取肝脏组织提取mRNA。运用基因芯片技术分析胰岛素信号通路相关的108个靶基因的mRNA表达。结果设定A组的mRNA表达为100%,B组和C组的胰岛素信号通路相关基因表达改变如下:①蛋白激酶B(Akt)-2分别为26%和63%,Akt-3分别为17%和71%,磷脂酰肌醇-3激酶调节亚基2(PIK3R2)分别为241%和97%,蛋白酪氨酸磷酸酶N1基因(PTPN1)分别为293%和143%;②Cbl相关蛋白(Cap)分别为38.77%和63.60%,Cbl分别为34.48%和67.85%,Crk分别为27.49%和36.06%;③Shc3分别为526.8%和260.6%,SOS1分别为203.0%和79.29%。结论外源性胰岛素干预通过上调Akt-2、Akt-3的表达、下调PIK3R2和PTPN1的表达改善磷脂酰肌醇3激酶(PI3K)信号通路;应用外源性胰岛素没有增强胰岛素抵抗小鼠胰岛素促有丝分裂通路的转导。

Objective To explore the effect of exogenous insulin intervention on insulin signal pathway in the liver tissue of diabetic mice. Methods 5-week-old C57BL/6 mice were randomized divided into 3 groups： Group A, the mice were fed with normal diet; Group B and C, the mice were fed with high fat diet. After 12 weeks＇ feeding, mice in group C were injected with insulin glargine at 0. 5 IU/d. After 4 weeks＇ intervention, liver tissues of the mice were frozen for mRNA extraction. The mRNA expression of 108 target genes involved in insulin signaling pathway were detected by gene microari-ay. Results If the mRNA expression in Group A was 100%, the expression of genes involved in the insulin signaling pathway of Group B and C were as follows ： ①Akt-2 26% and 63%, Akt-3 17% and 71%, Phosphoinositide-3-kinase（PI3K） regulatory subunit polypeptide 2（PIK3R2） 241% and 97%, PTPN1 293% and 143% ;②Cap 38. 77% and 63.60% , Cbl 34. 48% and 67.85% , Crk 27.49% and 36. 06% ; ③Shc3 526. 8% and 260. 6% ; SOS1 203.0% and 79.29% respectively. Conclusions Exogenous insulin improved PI3K signaling by up-regulation of Akt-2 and Akt-3 and down-regulation of PIK3R2 and PTPN1. Systemic use of insulin might not aggravate insulin action of mitogenic pathway.