Disease relevance of SGLT1

• Heat stress (HS) induces activation of high-affinity sodium-dependent glucose transporter (SGLT1) in porcine renal LLC-PK(1) cells [1].
• Feed intake and weight gain were monitored throughout; in vivo nutrient absorption, in vitro nutrient transport, sodium-glucose cotransporter activity, and intestinal morphology (gross and microscopic) were examined at the end of treatment [2].

High impact information on SGLT1

• SGLT1 mRNA levels were highest when the D-glucose concentration in the culture medium was 5 to 10 mM [3].
• The extensive homology of the two sequences leads us to suggest that the high-affinity SGLT expressed by LLC-PK1 cells is SGLT1 [3].
• To identify the sodium-coupled glucose transporter (SGLT), we cloned and sequenced several partial cDNAs homologous to SGLT1 from rabbit small intestine (M. A. Hediger, M. J. Coady, T. S. Ikeda, and E. M. Wright, Nature (London) 330:379-381, 1987) [3].
• SGLT1 activity, measured by methyl alpha-D-glucopyranoside uptake, paralleled message levels except in cultures containing D-galactose [3].
• Addition of D-mannose or D-fructose, but not D-galactose, in the presence of 5 mM D-glucose suppressed SGLT1 mRNA levels [3].

Biological context of SGLT1

• Transfection of an anti-Hsp70 antibody into the cells inhibited the increase of SGLT1 activity [4].
• These results suggest that Hsp70 forms a complex with SGLT1 and increases the expression level of SGLT1 in the apical membrane, resulting in up-regulation of glucose uptake [4].
• Aminoglycoside antibiotics reduce glucose reabsorption in kidney through down-regulation of SGLT1 [5].
• Previous studies on the small intestinal brush border membrane have shown that part of the decrease in the activity of the Na(+)-dependent glucose transporter (SGLT1) observed after oxidation could be secondary to the derangement in membrane fluidity that accompanied oxidative damage [6].
• Therefore, SGLT1 gene expression may respond either to the cellular energy status or to the concentration of a hexose metabolite(s) [3].

Anatomical context of SGLT1

• RS1 altered the expression of Na(+)-glucose cotransport by SGLT1 in Xenopus oocytes [7].
• Apolipoprotein E3 (apoE3) safeguards pig proximal tubular LLC-PK1 cells against reduction in SGLT1 activity induced by gentamicin C [8].
• At least two types of glucose transporter exist in cultured renal epithelial cells, a Na(+)-glucose cotransporter (SGLT), capable of interacting with D-glucose but not 2-deoxy-D-glucose (2dglc) and a facilitated transporter (GLUT) capable of interacting with both D-glucose and 2dglc [9].
• Recently a member of the Na+/glucose (SGLT1) gene family of cotransporters was isolated from a pig renal cell line and was thought to be the neutral amino acid transporter System A [10].
• In this study, we investigated the roles of SGLT1 activation in reorganization of zonula occludens-1 (ZO-1), a cytosolic tight junction (TJ) protein, after HS [1].

Associations of SGLT1 with chemical compounds

• We investigated whether sodium-dependent glucose transporter (SGLT1) interacts with Hsp70 to increase SGLT1 activity [4].
• To obtain evidence about SGLT1 down-regulation in vivo, we studied the mRNA expression of SGLT1 using gentamicin C-treated murine kidney and found that gentamicin C down-regulated SGLT1 in vivo as well as in vitro [5].
• Then the cells were treated with various concentrations of apoE3, lactoferrin and bovine serum albumin with or without 100 microg/ml of GMC, and the SGLT1-dependent methyl alpha-D-glucopyranoside (AMG) uptake and levels of SGLT1 expression were determined [8].
• During growth to confluence, 2dglc uptake increased to a maximum, then decreased at the time of confluence, coincident with a rise in uptake capacity for alpha-methyl-D-glucoside, a hexose that interacts only with the apical SGLT [9].
• Specific glucose transport inhibitor studies using phlorizin, phloretin and cytochalasin B confirmed the polarised distribution of SGLT and GLUT in LLC-PK1 cells [9].

Regulatory relationships of SGLT1

• As a result, we found that the aminoglycosides significantly reduced Na(+)/glucose cotransporter (SGLT1)-dependent glucose transport and also down-regulated mRNA and protein levels of the SGLT1 in pig proximal tubular LLC-PK(1) cells [5].
• Anti-transforming growth factor-beta 1 (TGF-beta 1) antibody inhibited both elevation of SGLT1 distribution in apical membrane and recovery of calcein accumulation induced by HS [11].

Other interactions of SGLT1

• We previously reported that aminoglycoside antibiotics reduce SGLT1-dependent glucose transport in pig proximal tubular epithelial LLC-PK1 cells in parallel with the order of their nephrotoxicity [8].
• Previously we cloned membrane associated (M(r) 62000-67000) polypeptides from pig (pRS1), rabbit (rbRS1) and man (hRS1) which modified transport activities that were expressed in Xenopus laevis oocytes by the Na(+)-D-glucose cotransporter SGLT1 and/or the organic cation transporter OCT2 [12].
• Biophysical characteristics of the pig kidney Na+/glucose cotransporter SGLT2 reveal a common mechanism for SGLT1 and SGLT2 [13].
• Taken together, HS increases in the number of SGLT1 protein in apical membrane mediated via TGF-beta 1 signaling pathway [11].

Analytical, diagnostic and therapeutic context of SGLT1

• SGLT1 mRNA levels were significantly increased after treatment of confluent cultures with HMBA, paralleling increases in the transport activity and immunodetectable 75 kD cotransporter subunit [14].
• Northern blot and PCR analysis of clonal cell populations indicated SGLT1 mRNA was not detectable in subconfluent cultures, but 2.2 and 3.9 kb SGLT1 mRNA species appeared after cell confluence, accompanying expression of the transport activity [14].
• RESULTS: Western blot analysis clearly demonstrated the presence of Na-K-ATPase, NKCC1 and SGLT1 proteins in both bulbar and palpebral conjunctiva [15].
• METHODS: Mouse monoclonal antibodies against the alpha1-subunit of Na-K-ATPase and Na-K-Cl cotransporter (NKCC1) and a rabbit polyclonal antibody against the Na-glucose cotransporter (SGLT1) were used in immunoblotting and immunofluorescent labeling of frozen fixed sections isolated from either the bulbar and palpebral regions of the conjunctiva [15].
• Expression of the Na(+)/glucose cotransporter-1 (SGLT-1) was assayed in PAECs and PCA endothelium by RT-PCR [16].

References