Kalsi Kameljit K, Baker Emma H, Medina Rodolfo A, Rice Suman, Wood David M, Ratoff Jonathan C, Philips Barbara J, Baines Deborah L
Centre for Ion Channel and Cell Signalling, Division of Basic Medical Sciences, St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK.
Pflugers Arch. 2008 Aug;456(5):991-1003. doi: 10.1007/s00424-008-0459-8. Epub 2008 Feb 1.
Glucose concentrations of normal human airway surface liquid are approximately 12.5 times lower than blood glucose concentrations indicating that glucose uptake by epithelial cells may play a role in maintaining lung glucose homeostasis. We have therefore investigated potential glucose uptake mechanisms in non-polarised and polarised H441 human airway epithelial cells and bronchial biopsies. We detected mRNA and protein for glucose transporter type 2 (GLUT2) and glucose transporter type 4 (GLUT4) in non-polarised cells but GLUT4 was not detected in the plasma membrane. In polarised cells, GLUT2 protein was detected in both apical and basolateral membranes. Furthermore, GLUT2 protein was localised to epithelial cells of human bronchial mucosa biopsies. In non-polarised H441 cells, uptake of D: -glucose and deoxyglucose was similar. Uptake of both was inhibited by phloretin indicating that glucose uptake was via GLUT-mediated transport. Phloretin-sensitive transport remained the predominant route for glucose uptake across apical and basolateral membranes of polarised cells and was maximal at 5-10 mM glucose. We could not conclusively demonstrate sodium/glucose transporter-mediated transport in non-polarised or polarised cells. Our study provides the first evidence that glucose transport in human airway epithelial cells in vitro and in vivo utilises GLUT2 transporters. We speculate that these transporters could contribute to glucose uptake/homeostasis in the human airway.
正常人呼吸道表面液体中的葡萄糖浓度比血糖浓度低约12.5倍，这表明上皮细胞摄取葡萄糖可能在维持肺部葡萄糖稳态中发挥作用。因此，我们研究了非极化和极化的H441人气道上皮细胞及支气管活检组织中潜在的葡萄糖摄取机制。我们在非极化细胞中检测到了2型葡萄糖转运蛋白（GLUT2）和4型葡萄糖转运蛋白（GLUT4）的mRNA和蛋白，但在质膜中未检测到GLUT4。在极化细胞中，在顶端和基底外侧膜中均检测到了GLUT2蛋白。此外，GLUT2蛋白定位于人支气管黏膜活检组织的上皮细胞中。在非极化的H441细胞中，D-葡萄糖和脱氧葡萄糖的摄取相似。二者的摄取均被根皮素抑制，这表明葡萄糖摄取是通过GLUT介导的转运。根皮素敏感的转运仍然是极化细胞顶端和基底外侧膜葡萄糖摄取的主要途径，并且在5-10 mM葡萄糖浓度下达到最大值。我们无法确凿地证明非极化或极化细胞中存在钠/葡萄糖转运蛋白介导的转运。我们的研究首次证明，体外和体内人气道上皮细胞中的葡萄糖转运利用GLUT2转运蛋白。我们推测这些转运蛋白可能有助于人类气道中的葡萄糖摄取/稳态。
