Barry James S, Davidsen Meredith L, Limesand Sean W, Galan Henry L, Friedman Jacob E, Regnault Timothy R H, Hay William W
Department of Pediatrics, Section of Neonatology, University of Colorado School of Medicine, The Children's Hospital, 1056 East 19th Avenue, Box B070, Denver, CO 80218, USA.
Exp Biol Med (Maywood). 2006 May;231(5):566-75. doi: 10.1177/153537020623100511.
Developmental changes in ovine myocardial glucose transporters and insulin signaling following hyperthermia-induced intrauterine fetal growth restriction (IUGR) were the focus of our study. Our objective was to test the hypothesis that the fetal ovine myocardium adapts during an IUGR gestation by increasing glucose transporter protein expression, plasma membrane-bound glucose transporter protein concentrations, and insulin signal transduction protein concentrations. Growth measurements and whole heart tissue were obtained at 55 days gestational age (dGA), 90 dGA, and 135 dGA (term = 145 dGA) in fetuses from control (C) and hyperthermic (HT) pregnant sheep. Additionally, in 135 dGA animals, arterial blood was obtained and Doppler ultrasound was used to determine umbilical artery systolic (S) and diastolic (D) flow velocity waveform profiles to calculate pulsatility (S - D/mean) and resistance (S - D/S) indices. Myocardial Glut-1, Glut-4, insulin signal transduction proteins involved in Glut-4 translocation, and glycogen content were measured. Compared to age-matched controls, HT 90-dGA fetal body weights and HT 135-dGA fetal weights and gross heart weights were lower. Heart weights as a percent of body weights were similar between C and HT sheep at 135 dGA. HT 135-dGA animals had (i) lower fetal arterial plasma glucose and insulin concentrations, (ii) lower arterial blood oxygen content and higher plasma lactate concentrations, (iii) higher myocardial Glut-4 plasma membrane (PM) protein and insulin receptor beta protein (IRbeta ) concentrations, (iv) higher myocardial glycogen content, and (v) higher umbilical artery Doppler pulsatility and resistance indices. The HT ovine fetal myocardium adapts to reduced circulating glucose and insulin concentrations by increasing plasma membrane Glut-4 and IRbeta protein concentrations. The increased myocardial Glut-4 PM and IRbeta protein concentrations likely contribute to or increase the intracellular delivery of glucose and, together with the increased lactate concentrations, enhance glycogen synthesis, which allows for maintained myocardial growth commensurate with fetal body growth.
热应激诱导的宫内胎儿生长受限（IUGR）后绵羊心肌葡萄糖转运体和胰岛素信号转导的发育变化是我们研究的重点。我们的目的是检验以下假设：在IUGR妊娠期间，胎儿绵羊心肌通过增加葡萄糖转运体蛋白表达、质膜结合葡萄糖转运体蛋白浓度和胰岛素信号转导蛋白浓度来适应。在来自对照（C）和热应激（HT）妊娠绵羊的胎儿中，于妊娠55天（dGA）、90 dGA和135 dGA（足月=145 dGA）时获取生长测量数据和全心脏组织。此外，在135 dGA的动物中，采集动脉血并使用多普勒超声确定脐动脉收缩期（S）和舒张期（D）血流速度波形图，以计算搏动性（S - D/平均）和阻力（S - D/S）指数。测量心肌Glut-1、Glut-4、参与Glut-4易位的胰岛素信号转导蛋白以及糖原含量。与年龄匹配的对照组相比，HT 90 dGA胎儿体重以及HT 135 dGA胎儿体重和心脏总重量较低。在135 dGA时，C组和HT组绵羊心脏重量占体重的百分比相似。HT 135 dGA动物具有以下特征：（i）胎儿动脉血浆葡萄糖和胰岛素浓度较低；（ii）动脉血氧含量较低且血浆乳酸浓度较高；（iii）心肌Glut-4质膜（PM）蛋白和胰岛素受体β蛋白（IRbeta）浓度较高；（iv）心肌糖原含量较高；（v）脐动脉多普勒搏动性和阻力指数较高。HT绵羊胎儿心肌通过增加质膜Glut-4和IRbeta蛋白浓度来适应循环葡萄糖和胰岛素浓度的降低。心肌Glut-4 PM和IRbeta蛋白浓度的增加可能有助于或增加葡萄糖的细胞内转运，并且与增加的乳酸浓度一起，增强糖原合成，从而使心肌生长与胎儿身体生长相适应得以维持。
