Distinct distribution of GLUT4 and insulin regulated aminopeptidase in the mouse kidney

Distinct distribution of GLUT4 and insulin regulated aminopeptidase in the mouse kidney
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DOI:
10.1016/j.regpep.2010.09.003
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发表时间:
2011-01-17
影响因子:
--
通讯作者:
Chai, Siew Yeen
Chai, Siew Yeen
中科院分区:
其他
文献类型:
--
作者:
Albiston, Anthony L.;Yeatman, Holly R.;Chai, Siew Yeen

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脂肪细胞和肌肉中胰岛素反应性葡萄糖转运体GLUT4在维持葡萄糖稳态中的生理重要性已得到充分证实。与这一过程相关的一个关键蛋白是氨基肽酶IRAP,它与GLUT4在特殊的囊泡中共定位,在那里它起着栓系作用。在这项研究中,我们研究了GLUT4和IRAP在肾脏中的分布,以深入了解这些蛋白质在该器官中的潜在作用。大鼠皮层近端、远端小管及粗升肢上皮细胞均可见IRAP和GLUT4免疫染色,但GLUT4和IRAP免疫反应性很少重叠。GLUT4染色与囊泡定位一致,而IRAP染色主要在腔内。表面。在髓质内集管(IMCD)的主要细胞中,整个细胞都检测到IRAP的免疫反应性,与抗利尿激素应答水通道水通道蛋白-2 (AQP-2)有有限的重叠。在IRAP基因敲除小鼠中,AQP-2水平升高了两倍。基于我们的结果,我们提出GLUT4在上皮细胞间的葡萄糖分流中起作用。在肾皮质中,IRAP与其他肽酶可能在生成供摄取的游离氨基酸中起重要作用,而在髓质内的主要细胞中,IRAP可能在调节抗利尿激素的生物活性中起局部作用。(C) 2010 Elsevier B.V.版权所有
The physiological importance of the insulin responsive glucose transporter GLUT4 in adipocytes and muscle in maintaining glucose homeostasis is well established. A key protein associated with this process is the aminopeptidase IRAP which co-localizes with GLUT4 in specialized vesicles, where it plays a tethering role. In this study, we investigated the distribution of both GLUT4 and IRAP in the kidney to gain insights into the potential roles of these proteins in this organ. Both IRAP and GLUT4 immunostaining was observed in the epithelial cells of the proximal and distal tubules and thick ascending limbs in the cortex, but very little overlap between GLUT4 and IRAP immunoreactivity was observed. GLUT4 staining was consistent with a vesicular localization, whereas IRAP staining was predominantly on the lumina! surface. In the principal cells of the inner medulla collecting duct (IMCD), IRAP immunoreactivity was detected throughout the cell, with limited overlap with the vasopressin responsive water channel aquaporin-2 (AQP-2). AQP-2 levels were observed to be two-fold higher in IRAP knockout mice. Based on our results, we propose that GLUT4 plays a role in shunting glucose across epithelial cells. In the kidney cortex, IRAP, in concert with other peptidases, may be important in the generation of free amino acids for uptake, whereas in the principal cells of the inner medulla IRAP may play a localized role in the regulation of vasopressin bioactivity. (C) 2010 Elsevier B.V. All rights reserved.