MOLECULAR ADAPTATIONS OF GLUT1 AND GLUT2 IN RENAL PROXIMAL TUBULES OF DIABETIC RATS
MOLECULAR ADAPTATIONS OF GLUT1 AND GLUT2 IN RENAL PROXIMAL TUBULES OF DIABETIC RATS
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DOI：
10.1152/ajprenal.1994.266.2.f283
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发表时间：
1994-02-01
影响因子：
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通讯作者：
GARVEY, WT
中科院分区：
文献类型：
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作者：
DOMINGUEZ, JH;CAMP, K;GARVEY, WT
肾脏对葡萄糖的重吸收是由两类主要的转运蛋白介导的。最初，腔内葡萄糖通过Na+-葡萄糖共转运体(Na+-GLUT)集中在小管中。然后，葡萄糖通过促进性葡萄糖转运蛋白、低米氏常数(K-m)GLUT1和高K-m GLUT2进入血液空间。因此，在高血糖时，通过肾小管的葡萄糖流量可能会受到损害，因为从肾小管到血液的外向葡萄糖梯度可能会降低。然而，在糖尿病大鼠中，经肾小管葡萄糖流量不仅没有减少，反而增加了。在这项工作中，研究了这种适应的分子机制。我们验证了这样的假设，即肾小管高K-m谷氨酸氨基转移酶基因的上调可以补偿肾小管到血糖梯度的降低。在未加控制的链脲佐菌素诱导的糖尿病2周、3周和4周后，大鼠肾小管中GLUT1蛋白和mRNA的稳态水平降低，而GLUT2蛋白和mRNA的水平升高。这些分子适应与增强的促进性葡萄糖流量有关。综上所述，GLUT1和GUTS基因表达的变化对高血糖状态下肾脏葡萄糖重吸收的保存具有重要意义。
The renal reabsorption of glucose is mediated by two major classes of transporters. Initially, luminal glucose is concentrated in tubules by Na+-glucose cotransporters (Na+-GLUT). Afterwards, glucose reaches the blood space through facilitative glucose transporters, low-Michaelis constant (K-m) GLUT1 and high-K-m GLUT2. Hence, the transtubular flux of glucose could be impaired in hyperglycemia because the outwardly directed glucose gradient, from tubule to blood, is potentially lowered. However, in diabetic rats, transtubular glucose flux is not reduced but increased. In this work the molecular mechanism underlying this adaptation was examined. We tested the hypothesis that upregulation of renal tubular high-K-m GLUTS gene may compensate for the decrease in the tubule to blood glucose gradient. In rat tubules, GLUT1 protein and mRNA steady-state levels were reduced, and GLUT2 protein and mRNA levels were increased in rats after 2, 3, and 4 wk of uncontrolled streptozotocin-induced diabetes. These molecular adaptations were associated with augmented facilitative glucose flux. In summary, changes in GLUT1 and GLUTS gene expression are important to the preservation of renal glucose reabsorption in hyperglycemia.