胎儿生长受限仔鼠脂肪组织中葡萄糖转运蛋白4的表达和细胞转位变化

Glucose transporter 4 expression and translocation in adipose tissue of male rats born with fetal growth restriction

目的探讨胎儿生长受限（FGR）仔鼠脂肪组织中葡萄糖转运蛋白4（GLUT4）的表达和转位变化及其与胰岛素抵抗的关系。方法采用妊娠期全程低蛋白饮食法建立大鼠FGR模型，并设立对照组。观察雄性仔鼠生后体重增长和胰岛素抵抗指数（IRI）变化，采用荧光定量逆转录聚合酶链反应技术检测脂肪组织中GLUT4mRNA表达，Western印迹法检测基础状态下脂肪组织中GLUT4的蛋白表达，以及胰岛素刺激后GLUT4向细胞膜的转位变化。结果（1）FGR组仔鼠平均出生体重明显低于对照组（t=6．399，P〈0．01），8周龄时体重超过对照组，且空腹IRI增高（P均〈0．05）。（2）基础状态下，FGR组脂肪组织中GLUT4的mRNA表达（0．36±0．04）明显低于对照组（1．01±0．11）（t=2．854，P〈0．05），GLUT4总蛋白含量（913．47±87．32）也低于对照组（1248．30±131．52）（t=2．617，P〈0．05）。胰岛素刺激后，对照组细胞膜中GLUT4蛋白浓度显著升高（897．03±102．87），是基础状态（423．05±41．26）的2．12倍（t=4．759，P〈0．01），而FGR组对外源性胰岛素反应迟钝，细胞膜中GLUT4蛋白含量（525．12±54．96）仅是基础状态（379．57±38．71）的1．38倍（t=2．083，P〈0．05）。结论宫内蛋白质营养不良导致子代脂肪组织GLUT4蛋白表达降低和胰岛素介导的转位受阻，可能与葡萄糖摄取和利用障碍，促进糖尿病发生有关。

Objective To investigate the effects of fetal growth restriction （FGR） on the expressions and translocation of glucose transporter 4 （GLUT4） in adipose tissue of male offsprings and its relationship with insulin resistance in FGR. Methods Male 8-week-old offspring from maternal with protein- malnutrition or normal diet were studied. The weight of rats at 8 weeks of age were obtained and insulin resistance index （IRI） was examined at 4 weeks and 8 weeks of age. Perinephric fat pads were harvested to measure the expression of GLUT4 mRNA by fluorescent quantitative RT-PCR and the GLUT4 protein level and insulin-stimulated translocation were assessed by Western blot. Results Birth weight of FGR animals were significantly lower than that of control （t= 6. 399, P〈0.01）, but surpassed the control at 8 weeks with increased fasting IRI（P〈0. 05）. The GLUT4 mRNA expression in adipose tissue of FGR rats （0. 36±0. 04） was lower than that of control （1.01±0. 11） （t=2. 854, P〈0. 05）. Declined total GLUT4 protein concentration（913.47±87.32） was also noted in the FGR group compared with the controls （1248. 30±131.52） （t = 2. 617, P 〈 0. 05） . After administration of insulin, plasma membrane associated-GLUT4 concentration significantly increased to 897. 03±102. 87, which was equal to 2. 12 times of the basal level （423.05±41.26） in control rats（t=4. 759, P〈0. 01）. However, insulin-responsive GLUT4 translocation was markedly blunted in FGR rats（525.12±54.96） compared with controls, only increased to 1.38 times of the basal level （379.57±38. 71）（t=2. 083, P〈0. 05）. Conclusions Decreased GLUT4 expression and insulin-stimulated translocation in adipose tissue of the male FGR offspring might be caused by exposure to protein malnutrition during pregnancy, which may disturb the uptake and utilization of glucose and subsequently be related to diabetes mellitus in later life.