T1R3 and GLUT2 are predominantly expressed in subsets of solitary chemoreceptor cells (SCCs) and ciliated cells, GLUT5 is present in subsets of SCCs and in secretory cells, and SGLT1 is exclusively expressed in a unique cell type, SCCs. cell type, SCCs. Furthermore, we exhibited that T1R3 is usually colocalized with SGLT1 in SCCs and with GLUT2 transporter in ciliated cells. In conclusion, these findings reveal that different cell types are associated with the uptake of glucose in ASL and that, due to their T1R3 expression, SCCs and ciliated cells are most likely to participate in the chemosensory process in ASL. G-protein coupled taste receptors and their downstream signaling molecules, through mechanisms analogous to those known to occur in TRCs and in epithelia involved in the monitoring/uptake of the luminal content and in glucose sensing (i.e. intestinal epithelium and pancreatic cells, respectively). The functional significance of T1R3 expression in more than one site around the ciliated cells requires further study. Non-ciliated cellsIn this research Butein we observed intense immunostaining for GLUT5 in the apical membrane Butein of non-ciliated epithelial cells (identified as secretory cells by their morphological characteristics) and in some basal cells. Even though paucity of data on GLUT5 presence in airway epithelium makes it impossible to draw any conclusions regarding the significance of GLUT5 expression in the trachea, the most likely hypothesis issues control of fructose in ASL, since GLUT5 is usually its specific transporter. Recently, the simultaneous presence in subsets of secretory cells of chemosensory (i.e. -gustducin and PLC2) and secretory (i.e. cystic fibrosis transmembrane regulator and Clara cell secretory protein) markers has been interpreted as an ability of these cells to respond to exogenous stimuli with secretory events, suggesting the possibility of ultra-short (intracellular) reflexes in the control of airway secretion (Merigo et al. 2007). Because GLUT5 expression is unique to this cell type, it could be useful to investigate its role in secretory function. General conclusion Although it is not yet obvious what roles sugars have in the airway, the physiological function of glucose transporters is mainly associated with the maintenance of low sugar concentration in ASL (Mager & Sloan, 2003). This has been shown to preserve mucociliary clearance and to protect against bacterial colonization or contamination in humans and rodents (Baker et al. 2006; Pezzulo et al. 2011). Elevated airway glucose concentration has been regarded as an expression of impaired glucose homeostasis, since experimental and clinical evidence shows that it correlates closely with blood hyperglycaemia (Solid wood et al. 2004; Clark et al. 2006), which increases paracellular diffusion of glucose from blood to ASL (Baker et al. 2006). A recent study highlighted an interesting regulatory effect of ASL glucose concentration on mucosal uptake, showing that increased absorption by the cells lining the tracheal lumen was caused by greater passive diffusion of glucose (Kalsi et al. 2008b), suggesting an ability of the mucosa to sense the glucose concentrations in ASL. However, little is currently known about the mechanism involved in transmission transmission from your ASL to the airway epithelium. Understanding of this mechanism would require knowledge of where and how sugar is sensed, and how changes in ASL glucose levels are communicated to the downstream signaling cascade. The presence of T1R3 and GLUT-transporters at the apical membrane of tracheal cells implies that the effective local glucose/hexose concentrations may be in the range of sugar receptor and transporter activity. The determination of such concentrations can be an important important to understanding the role of glucose transporters and receptors on glucose homeostasis in ASL. Close matching found between glucose transporter expression and luminal sugar content in the intestine contributed to the emergence of many aspects of the regulation and activity of glucose transporters (Kellett & Brot-Laroche, 2005; Dyer et al. 2007). Similarly, we believe that the current findings may contribute to clearer identification of some of the players which take part in sugar uptake in the trachea. The diagram in Fig. 11 summarizes the cellular distribution of glucose transporters and T1R3 that we observed. Because of their T1R3 expression, SCCs and ciliated cells are the candidates Smad3 most likely to participate in the chemosensory process in ASL. Open Butein in a separate windows Fig. 11 The diagram shows a simplified summary of glucose transporters (GLUT2, GLUT5, SGLT1) and T1R3 immunolocalization in different cell.
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