Thyroid hormone regulation of the Na+/glucose cotransporter SGLT1 in Caco-2 cells.
The expression of the Na+/glucose cotransporter (SGLT1) in response to thyroid hormone [3,5,3'-tri-iodo-l-thyronine (T3)] was investigated in the enterocytic model cell line Caco-2/TC7. In differentiated cells, T3 treatment induces an average 10-fold increase in glucose consumption as well as a T3 dose-dependent increase in SGLT1 mRNA abundance. Only cells grown on glucose-containing media, but not on the non-metabolizable glucose analogue alpha-methylglucose (AMG), could respond to T3-treatment. The Vmax parameter of AMG transport was enhanced 6-fold by T3 treatment, whereas the protein abundance of SGLT1 was unchanged. The role of Na+ recycling in the T3-related activation of SGLT1 activity was suggested by both the large increase in Na+/K+ATPase protein abundance and the inhibition, down to control levels, of AMG uptake in ouabain-treated cells. Further investigations aimed at identifying the presence of a second cotransporter that could be expressed erroneously in the colon cancer cell line were unsuccessful: T3-treatment did not modify the sugar-specificity profile of AMG transport and did not induce the expression of SGLT2 as assessed by reverse transcription-PCR. Our results show that T3 can stimulate the SGLT1 cotransport activity in Caco-2 cells. Both transcriptional and translational levels of regulation are involved. Finally, glucose metabolism is required for SGLT1 expression, a result that contrasts with the in vivo situation and may be related to the fetal phenotype of the cells.
Matosin-Matekalo
M
M
Unité de Recherches sur la Différenciation Cellulaire Intestinale, INSERM U178, 16 avenue Paul-Vaillant-Couturier, 94807 Villejuif Cedex, France.
Mesonero
J E
JE
Delezay
O
O
Poiree
J C
JC
Ilundain
A A
AA
Brot-Laroche
E
E
D001483:Base Sequence; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D008757:Methylglucosides / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000378:metabolism*; D051269:Sodium-Glucose Transporter 1; D051297:Sodium-Glucose Transporter 2; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*
D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495674:SLC5A1 protein, human; C089180:SLC5A2 protein, human; D051269:Sodium-Glucose Transporter 1; D051297:Sodium-Glucose Transporter 2; D014284:Triiodothyronine; C027020:methylglucoside; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose