Time-dependent and tissue-specific effects of circulating glucose on fetal ovine glucose transporters
Time-dependent and tissue-specific effects of circulating glucose on fetal ovine glucose transporters
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DOI：
10.1152/ajpregu.1999.276.3.r809
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发表时间：
1999-03-01
影响因子：
2.8
通讯作者：
Devaskar, SU
中科院分区：
文献类型：
--
作者：
Das, UG;Schroeder, RE;Devaskar, SU
为了确定细胞对胎儿高血糖和低血糖的适应性，我们通过定量蛋白质印迹分析，在胎儿绵羊胰岛素不敏感（脑和肝脏）和胰岛素敏感（心肌、骨骼肌和脂肪）组织中，研究了对基础（GLUT-1和GLUT-3）和胰岛素响应（GLUT-4）葡萄糖转运蛋白的时间依赖性影响。与胎龄匹配的对照组相比，母体葡萄糖输注导致胎儿高血糖导致脑GLUT-1水平一过性升高30%，但GLUT-3水平未升高，肝脏和脂肪GLUT-1以及心肌和骨骼肌GLUT-1和GLUT-4水平下降。与胎龄匹配的假手术对照组相比，母体胰岛素输注导致胎儿低血糖导致脑GLUT-2下降，脑GLUT-1增加，随后肝GLUT-1下降，胰岛素敏感心肌、骨骼肌和脂肪组织GLUT-1或GLUT-4浓度无显著变化。我们的结论是，胎儿葡萄糖转运蛋白是受时间依赖性和组织和亚型特异性差异调节，以改变循环葡萄糖和/或胰岛素浓度。GLUT-1（和GLUT-3）中的这些细胞适应是为了保护孕体免受底物可用性的干扰，而GLUT-4中的适应是为了发展胎儿胰岛素抵抗。
To determine the cellular adaptations to fetal hyperglycemia and hypoglycemia, we examined the time-dependent effects on basal (GLUT-1 and GLUT-3) and insulin-responsive (GLUT-4) glucose transporter proteins by quantitative Western blot analysis in fetal ovine insulin-insensitive (brain and liver) and insulin-sensitive (myocardium, skeletal muscle, and adipose) tissues. Maternal glucose infusions causing fetal hyperglycemia resulted in a transient 30% increase in brain GLUT-1 but not GLUT-3 levels and a decline in liver and adipose GLUT-1 and myocardial and skeletal muscle GLUT-1 and GLUT-4 levels compared with gestational age-matched controls. Maternal insulin infusions leading to fetal hypoglycemia caused a decline in brain GLUT-2, an increase in brain GLUT-1, and a subsequent decline in liver GLUT-1, with no significant change in insulin-sensitive myocardium, skeletal muscle, and adipose tissue GLUT-1 or GLUT-4 concentrations, compared with gestational age-matched sham controls. We conclude that fetal glucose transporters are subject to a time-dependent and tissue- and isoform-specific differential regulation in response to altered circulating glucose and/or insulin concentrations. These cellular adaptations in GLUT-1 (and GLUT-3) are geared toward protecting the conceptus from perturbations in substrate availability, and the adaptations in GLUT-4 are geared toward development of fetal insulin resistance.