宫内生长受限大鼠骨骼肌蛋白激酶B和葡萄糖转运蛋白4的表达和活性变化  

Expression and Activity of Protein Kinase B and Glucose Transporter 4 in Skeletal Muscles of the Intrauterine Growth Restriction Rats

作　　者：刘晓梅 焦伊胜[2] 潘莉莉[3] 卢岩[1] 李书琴[1] 

机构地区：[1]中国医科大学附属盛京医院实验研究中心,沈阳110004 [2]中国医科大学附属盛京医院妇产科,沈阳110004 [3]中国医科大学附属盛京医院检验科,沈阳110004

出　　处：《中国医科大学学报》2009年第2期105-107,共3页Journal of China Medical University

摘　　要：目的研究宫内营养不良造成的宫内生长受限(IUGR)子鼠骨骼肌中蛋白激酶B(PKB)和葡萄糖转运蛋白4(GLUT4)的表达和胰岛素诱导活性变化,探讨IUGR个体发生胰岛素抵抗的分子机制。方法通过妊娠期全程低蛋白饮食法建立大鼠IUGR模型,采用Westernblot方法检测雄性子鼠(8周)基础状态下骨骼肌PKB的表达和胰岛素刺激后磷酸化水平的变化,同时测定GLUT4的表达和胰岛素刺激后向细胞膜的转位。结果胰岛素刺激前后,IUGR鼠骨骼肌中PKB和磷酸化的PKBSer473表达水平都明显低于对照鼠(P<0.01),胰岛素刺激使对照组的PKBSer473磷酸化水平明显增加(P<0.01),IUGR组仅轻度增加。两组子鼠骨骼肌中总GLUT4的蛋白表达没有差别,胰岛素刺激后,对照组细胞膜中GLUT4蛋白浓度显著升高(P<0.01),IUGR组增高的幅度明显低于对照组(P<0.01)。结论宫内蛋白营养不良造成的IUGR鼠骨骼肌中PKB的表达和活性降低,导致胰岛素介导的GLUT4转位受阻,可能引起葡萄糖摄取和利用障碍,促进糖尿病发生。Objective To explore the molecular mechanisms of insulin resistance in intrauterine growth restriction （IUGR）, and to detect the effect of malnutrition in uterine on the expression and activity of protein kinase B （PKB） and glucose transporter 4 （GLUT4） in skeletal muscles. Methods Male offsprings from maternal protein-malnutrition dams were studied at 8 week. Western blot analysis was undertaken to assess basic expression of PKB and insulin-responsive increase in phosphorylated Ser473-PKB. GLUT4 expression and insulin-stimulated translocation were also assessed. Results Both PKB and phosphorylated Ser473-PKB protein levels were signilicantly decreased in liver of IUGR animals compared with the controls before and after administration of insulin （P 〈 0.01 ）. After administration of insuhn,phosphorylation at Ser1473 of PKB significantly increased in the control rats （P 〈 0.01 ）; however,phosphorylation of PKB responding to insulin was markedly blunted in IUGR rats compared with the controls. No significant differences were observed in basic levels of total GLUT4 protein. After insulin stimulation, plasma membrane associated- GLUT4 concentration significantly increased in the control rats （P 〈 0.01 ）.However, insulin-stimulated GLUT4 translocation was markedly depressed in IUGR rats compared with the controls （P 〈 0.01 ）. Conclusion Being exposed to protein malnutrition during pregnancy can decrease expression and activity of protein kinase B, and subsequently block GLUT4 insulin-stimulated translocation in the skeletal muscles, which may disturb the uptake and utilization of glucose and subsequently promote diabetes mellitus later in life.

关 键 词：宫内生长受限 胰岛素抵抗 蛋白激酶B 葡萄糖转运蛋白4 

分 类 号：R714[医药卫生—妇产科学]