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糖尿病中肠道刷状缘果糖转运适应过程中GLUT5和GLUT2活性的调节

The regulation of GLUT5 and GLUT2 activity in the adaptation of intestinal brush-border fructose transport in diabetes.

作者信息

Corpe C P, Basaleh M M, Affleck J, Gould G, Jess T J, Kellett G L

机构信息

Department of Biology, University of York, PO Box 373, York YO1 5YW, UK.

出版信息

Pflugers Arch. 1996 Jun;432(2):192-201. doi: 10.1007/s004240050124.

DOI:10.1007/s004240050124
PMID:8662294
Abstract

The adaptation of d-fructose transport in rat jejunum to experimental diabetes has been studied. In vivo and in vitro perfusions of intact jejunum with d-fructose revealed the appearance of a phloretin-sensitive transporter in the brush-border membrane of streptozotocin-diabetic rats which was not detectable in normal rats. The nature of the transporters involved was investigated by Western blotting and by d-fructose transport studies using highly purified brush-border and basolateral membrane vesicles. GLUT5, the major transporter in the brush-border membrane of normal rats, was not inhibited by d-glucose or phloretin. In contrast, GLUT2, the major transporter in the basolateral membrane of normal rats, was strongly inhibited by both D-glucose and phloretin. In brush-border membrane vesicles from diabetic rats, GLUT5 levels were significantly enhanced; moreover the presence of GLUT2 was readily detectable and increased markedly as diabetes progressed. The differences in stereospecificity between GLUT2 and GLUT5 were used to show that both transporters contributed to the overall enhancement of d-fructose transport measured in brush-border membrane vesicles and in vitro isolated loops from diabetic rats. However, overall d-fructose uptake in vivo was diminished. The underlying mechanisms and functional consequences are discussed.

摘要

已对大鼠空肠中d-果糖转运对实验性糖尿病的适应性进行了研究。用d-果糖对完整空肠进行体内和体外灌注发现,链脲佐菌素诱导的糖尿病大鼠的刷状缘膜中出现了一种根皮素敏感的转运体,而在正常大鼠中未检测到。通过蛋白质印迹法以及使用高度纯化的刷状缘膜和基底外侧膜囊泡进行d-果糖转运研究,对所涉及的转运体的性质进行了研究。GLUT5是正常大鼠刷状缘膜中的主要转运体,不受d-葡萄糖或根皮素的抑制。相比之下,GLUT2是正常大鼠基底外侧膜中的主要转运体,受到d-葡萄糖和根皮素的强烈抑制。在糖尿病大鼠的刷状缘膜囊泡中,GLUT5水平显著升高;此外,随着糖尿病的进展,GLUT2的存在很容易检测到且显著增加。利用GLUT2和GLUT5之间立体特异性的差异表明,这两种转运体都有助于糖尿病大鼠刷状缘膜囊泡和体外分离肠袢中d-果糖转运的总体增强。然而,体内d-果糖的总体摄取减少。文中讨论了潜在机制和功能后果。

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