Thyroid hormone regulation of the Na+/glucose cotransporter SGLT1 in Caco-2 cells

Abstract

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.

Thyroid hormone regulates the activity and expression of the peptide transporter PEPT1 in Caco-2 cells

“…In addition, the expression levels of PEPT1 mRNA and protein in Caco-2 cells were decreased by T 3 treatment. It was reported that treatment with thyroid hormone increased the expression of Na ϩ -K ϩ -ATPase ␣ 1 -protein and did not change the expression of SGLT1 protein in Caco-2 cells (16). In addition, the uptake of ␣-methyl-D-glucoside and threonine was not decreased by T 3 treatment (Fig.…”

“…Previously, Matosin-Matekalo et al (16) showed that T 3 treatment stimulated ␣-methyl-D-glucoside uptake via the Na ϩ -glucose cotransporter (SGLT1) in Caco-2 cells. Their observations were inconsistent with the present results.…”

“…Absorption of various nutritional substrates from the small intestine was shown to be altered in response to a thyroid state (14). Because 3,5,3Ј-L-triiodothyronine (T 3 ) is known to increase the metabolism of glucose, the effects of T 3 on the hexose transport systems in the small intestine (SGLT1, GLUT5) have been studied extensively (16,17). On the other hand, no information is available about the effects of T 3 on the absorption of oligopeptides, which are also important nutritional substrates.…”

SGLT Gene Expression in Primary Lung Cancers and Their Metastatic Lesions

“…The PCR primer sets for SGLT1 and SGLT2 and the procedure for PCR amplification were as described previously. 15) After predenaturation at 94°C for 5 min, the cDNA was added to 5 µl of the PCR mixture. 14) Amplification was carried out using a thermal cycler (Geneamp PCR System 2400; Perkin Elmer Applied Biosystems Division, Norwalk, CT).…”

An Essential Role of cAMP Response Element Binding Protein in Ginsenoside Rg1-Mediated Inhibition of Na+/Glucose Cotransporter 1 Gene Expression

“…SGLT1 expression has been shown to be controlled at both the transcription and translation levels as well as the posttranslational levels (Matosin-Matekalo et al, 1998;Loflin and Lever, 2001;Kekuda et al, 2008;Weihua et al, 2008). To examine the effect of Rg1 on SGLT1 protein or mRNA stability, Caco-2 cells were exposed to the protein synthesis inhibitor, cycloheximide, or the transcription inhibitor, actinomycin D. The results shown in Fig.…”