Changes in facilitative glucose transporter messenger ribonucleic acid levels in the diabetic rat kidney
Changes in facilitative glucose transporter messenger ribonucleic acid levels in the diabetic rat kidney
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DOI：
10.1210/en.138.3.1267
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发表时间：
1997-03-01
期刊：
影响因子：
4.8
通讯作者：
Bondy, CA
中科院分区：
文献类型：
--
作者：
Chin, E;Zamah, AM;Bondy, CA
促进性葡萄糖转运蛋白（GLUT1、GLUT2、GLUT4和glut5）信使rna （mrna）在大鼠肾细胞中的分布存在差异：GLUT1广泛表达，GLUT4选择性地集中在粗升肢，GLUT2和glut5仅局限于近端小管，这与这些转运蛋白在肾葡萄糖处理中的不同作用一致。在本研究中，采用定量原位杂交技术来评估急性（2和7天）和慢性（30、90和180天）链脲佐菌素诱导的糖尿病（STZ-DM）期间这些mRNA水平的变化。髓质GLUT1和GLUT4 mRNA水平在急性期显著升高，但在1周后恢复正常。然而，在STZ-DM的第7天至第6个月期间，皮质GLUT1 mRNA水平显著降低。在慢性STZ-DM中，皮质GLUT2 mRNA在急性期轻微升高，升高5倍，最大的升高集中在近端小管的卷曲部分。慢性STZ-DM期间近端小管GLUT5 mRNA水平也显著升高。总之，STZ-DM患者髓质GLUT1和GLUT4 mRNA水平急剧升高，与早期糖尿病患者肾上皮代谢活性升高相似。在慢性STZ-DM中，近端小管GLUT2和5 mRNA水平升高，可能是为了适应这些上皮细胞对葡萄糖转运的需求增加，而皮质GLUT1表达的减少可能反映了这些细胞对葡萄糖基底外侧进口需求的减少。因此，肾glut对STZ-DM的作用表现出复杂的、肾单元段特异性的和持续依赖性的反应。
Facilitative glucose transporter (GLUTs 1, 2, 4, and 5) messenger RNAs (mRNAs) are differentially distributed in the rat nephron: GLUT1 is widely expressed, GLUT4 is selectively concentrated in thick ascending limbs, and GLUT2 and 5 are exclusively localized in proximal tubules, consistent with differential roles for these transporters in renal glucose handling. In the present study, quantitative in situ hybridization was used to evaluate changes in these mRNA levels during acute (2 and 7 days) and chronic (30, 90, and 180 days) streptozotocin-induced diabetes mellitus (STZ-DM). Medullary GLUT1 and GLUT4 mRNA levels were significantly increased during the acute phase but returned to normal after 1 week. Cortical GLUT1 mRNA levels, however, were decreased significantly from 7 days through 6 months of STZ-DM. Cortical GLUT2 mRNA was slightly increased acutely and increased 5-fold in chronic STZ-DM, with the largest increase focally concentrated in the convoluted portion of the proximal tubule. Proximal tubule GLUT5 mRNA levels also were increased significantly during chronic STZ-DM.In summary, medullary GLUT1 and GLUT4 mRNA levels are acutely increased in STZ-DM, paralleling the increased renal epithelial metabolic activity accompanying early diabetes. Proximal tubular GLUT2 and 5 mRNA levels were increased in chronic STZ-DM, possibly adapting to the increased need for glucose transport out of these epithelial cells, whereas the concomitant decrease in cortical GLUT1 expression may reflect the decreased requirement for basolateral import of glucose into these same cells. Thus, renal GLUTs demonstrate complex, nephron segment-specific and duration-dependent responses to the effects of STZ-DM.