In:
American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 287, No. 4 ( 2004-10), p. C1041-C1047
Abstract:
We recently reported that a considerable amount of the sodium-d-glucose cotransporter SGLT1 present in Caco-2 cells, a model for human enterocytes, is located in intracellular compartments attached to microtubules (Kipp H, Khoursandi S, Scharlau D, and Kinne RKH. Am J Physiol Cell Physiol 285: C737–C749, 2003). A similar distribution pattern was also observed in enterocytes in thin sections from human jejunum, highlighting the validity of the Caco-2 cell model. Fluorescent surface labeling of live Caco-2 cells revealed that the intracellular compartments containing SGLT1 were accessible by endocytosis. To elucidate the role of endosomal SGLT1 in the regulation of sodium-dependent d-glucose uptake into enterocytes, we compared SGLT1-mediated d-glucose uptake into Caco-2 cells with the subcellular distribution of SGLT1 after challenging the cells with different stimuli. Incubation (90 min) of Caco-2 cells with mastoparan (50 μM), a drug that enhances apical endocytosis, shifted a large amount of SGLT1 from the apical membrane to intracellular sites and significantly reduced sodium-dependent α-[ 14 C]methyl-d-glucose uptake (−60%). We also investigated the effect of altered extracellular d-glucose levels. Cells preincubated (1 h) with d-glucose-free medium exhibited significantly higher sodium-dependent α-[ 14 C]methyl-d-glucose uptake (+45%) than did cells preincubated with high d-glucose medium (100 mM, 1 h). Interestingly, regulation of SGLT1-mediated d-glucose uptake into Caco-2 cells by extracellular d-glucose levels occurred without redistribution of cellular SGLT1. These data suggest that, pharmacologically, d-glucose uptake can be regulated by a shift of SGLT1 between the plasma membrane and the endosomal pool; however, regulation by the physiological substrate d-glucose can be explained only by an alternative mechanism.
Type of Medium:
Online Resource
ISSN:
0363-6143
,
1522-1563
DOI:
10.1152/ajpcell.00197.2004
Language:
English
Publisher:
American Physiological Society
Publication Date:
2004
detail.hit.zdb_id:
1477334-X
SSG:
12
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