Disease relevance of Slc5a1

• It is reported here that the renal brush-border membrane Na+/glucose co-transporter-1 (SGLT1) is a molecular target for Cd2+ toxicity [1].
• These results suggest that an increased SGLT1 expression concomitant with intestinal hypertrophy in OLETF rats is partly associated with postprandial hyperglycaemia before the onset of insulin resistance and hyperinsulinaemia [2].
• In this study, we examined the alterations of H(+)-peptide cotransporters (PEPT1 and PEPT2) and Na(+)-D-glucose cotransporters (SGLT1 and SGLT2) in chronic renal failure [3].
• These data indicate that SGLT-1 activity is regulated during hypoxia at the posttranslational level [4].
• To determine the contribution of hyperglycemia to the insulin resistance in various insulin-sensitive tissues of Zucker diabetic fatty (ZDF) rats, T-1095, an oral sodium-dependent glucose transporter (SGLT) inhibitor, was administered by being mixed into food [5].

Psychiatry related information on Slc5a1

• Refeeding for 2 d after 4 d of food deprivation returned the diurnal variation in SGLT1 and PEPT1 protein expressions to normal [6].
• Reports that food intake is stimulated by intracerebroventricular (i.c.v.) administration of the SGLT1 Na+-D-glucose cotransport inhibitor, phlorizin, suggest that decreased central glucose uptake is a stimulus for compensatory motor activity underlying restoration of energy imbalance [7].

High impact information on Slc5a1

• RESULTS: Reciprocal dose-response curves for the effects of the two hormones in intestine and liver were demonstrated: glucagon 37 was one order of magnitude more potent than glucagon 29 in increasing intestinal absorption of glucose via the SGLT1 [8].
• BACKGROUND & AIMS: Glucose and galactose are absorbed by the small intestine via the sodium-dependent glucose transporter 1 (SGLT1) and fructose via the facilitated glucose transporter 5 [8].
• Galactose transport and sodium-glucose/galactose-ligand transporter 1 (SGLT-1) expression were assessed in jejunal rings and in brush border membrane vesicles (BBMVs) [9].
• The expression of SGLT-1 on BBMVs (Western blot) and on the luminal membrane of enterocytes (immunohistochemistry) was not reduced in cirrhotic animals compared with controls or IGF-treated cirrhotic rats [9].
• In contrast, acarbose did not affect the transport rate of free D-fructose and did not inhibit 3-O-MG uptake in oocytes expressing sodium-glucose cotransporter 1 [10].

Chemical compound and disease context of Slc5a1

• RESULTS: Prenatal exposure of ethanol to rat pups leads to a decrease in their body weight, intestinal length and weight and reduces the uptake capacities of SGLT1 as well as energy dependent glycine and L-leucine transporters with respect to their age-matched controls [11].
• CONCLUSIONS: The observation that 3-o-mg did not differ from the mannitol control indicates that SGLT-1 activation alone does not exacerbate hypoxia [12].

Biological context of Slc5a1

• Luminal leptin induces rapid inhibition of active intestinal absorption of glucose mediated by sodium-glucose cotransporter 1 [13].
• In the present study, we examined the effects of various feeding conditions on the diurnal rhythm of intestinal SGLT1 and PEPT1 [6].
• Evidently the mechanism of absorption of quercetin-4'-glucoside involves both an interaction with SGLT1 and luminal hydrolysis by LPH, whereas quercetin-3-glucoside appears to be absorbed only following hydrolysis by LPH [14].
• These findings suggest that food intake, rather than the light cycle, greatly affects the diurnal rhythm of SGLT1 and PEPT1 expressions [6].
• These results suggest that a short amino acid sequence of the N-terminal domain of SGLT1 plays important roles in plasma membrane targeting and specific apical localization of the protein [15].

Anatomical context of Slc5a1

• High stringency Northern analysis demonstrated that SGLT1 is strongly expressed in small intestine and at lower levels in kidney, liver, and lung [16].
• Expression of rat SGLT1 in Xenopus oocytes resulted in a large Na(+)-dependent uptake of [14C]-alpha-methyl-D-glucopyranoside (alpha MeGlc) [16].
• METHODS: The presence of the GLUT isoforms and SGLT-1 in the endothelial cell layer was determined by immunohistochemistry using wide-field fluorescence microscopy coupled to deconvolution, and was quantified by digital image analysis [17].
• In micromolar concentrations, Cd2+ acted as a noncompetitive, partial inhibitor of methyl-D-glucopyranoside uptake in vesicles from COS-7 cells transiently expressing SGLT1 [1].
• AIMS/HYPOTHESIS: We have examined the effects of streptozotocin-induced type 1 diabetes on the expression and subcellular distribution of the classic sugar transporters (GLUT-1 to 5 and sodium-dependent glucose transporter-1 [SGLT-1]) in the endothelial cells of an en face preparation of septal coronary artery from Wistar rats [17].

Associations of Slc5a1 with chemical compounds

• We conclude that in the rat kidney, the expression of SGLT1 is represented by a 75-kDa protein localized largely in the PT S3 segments, where it exhibits gender differences (F > M) at both the protein and mRNA levels that are caused by androgen inhibition [18].
• To test the above hypotheses we employed phlorizin (as an inhibitor of SGLT1) and N-(n-butyl)-deoxygalactonojirimycin (as an inhibitor of the lactase domain of LPH) in a rat everted-jejunal sac model [14].
• Specifically, we assessed the quantitative relationships between lactose load and the series capacities of lactase and the Na+-glucose cotransporter (SGLT-1) [19].
• Xenopus oocytes were injected with RNA transcript encoding recombinant sodium-glucose cotransporter 1, and uptake of 3H-labeled 3-O-methyl-D-glucopyranose (3-O-MG) was assessed [10].
• Quercetin was a specific transport inhibitor, because it did not inhibit intestinal sugar transporters GLUT5 and SGLT1 that were injected and expressed in Xenopus oocytes [20].

Physical interactions of Slc5a1

• Upregulation of SGLT-1 transport activity in rat jejunum induced by GLP-2 infusion in vivo [21].

Regulatory relationships of Slc5a1

• Studies from our laboratory have demonstrated that leptin inhibits galactose absorption in vitro by acting on the Na(+)/glucose cotransporter SGLT1 [22].
• Hepatocyte growth factor up-regulates SGLT1 and GLUT5 gene expression after massive small bowel resection [23].
• These results indicate that GLP-2 is able to induce trafficking of SGLT-1 from an intracellular pool into the BBM within 60 min and that phosphoinositol 3-kinase may well be involved in the intracellular signaling pathway in this response [21].

Other interactions of Slc5a1

• To clarify whether the intestinal H(+)/peptide cotransporter (PEPT1) was expressed in the transplanted intestine, we examined the expression of PEPT1 in an experimental model of rat small intestinal transplantation in comparison with expression of Na(+)/glucose cotransporter (SGLT1) [24].
• Since PKC and PKA are involved in the regulation of SGLT1 and leptin is able to activate these kinases, we have investigated the possible implication of PKC and PKA in the inhibition of sugar absorption by leptin in rat small intestinal rings [22].
• Atrial natriuretic peptide and endothelin-3 target renal sodium-glucose cotransporter [25].
• In order to identify central cell populations that are functionally responsive to decreased SGLT1 function in the brain, the present study utilized immunocytochemical techniques to demonstrate cellular expression of the inducible activator protein-1 transcription factor, Fos, following i.c.v. delivery of phlorizin [7].
• Both the steady-state hexose absorption data and the washout studies indicated that the locus of action of CCK-8 was the SGLT1 transporter located in the brush-border membrane [26].

Analytical, diagnostic and therapeutic context of Slc5a1

• In situ hybridization performed on kidney sections revealed that SGLT1 is predominantly present in S3 segments of the proximal tubule [16].
• The functional relevance of SGLT1 for glucose transport across capillary walls in muscle was tested by measuring the extraction of D-glucose from the perfusate during non-recirculating perfusion of isolated rat hindlimbs [27].
• Northern blotting, Western blotting and immunohistochemistry were used to determine the effects of age on the BBM sodium-dependent glucose transporter, SGLT1, and the BLM Na+K(+)-ATPase [28].
• RESULTS: In the isografts, the levels of messenger RNA (mRNA) encoding both transporters were not changed, while the amount of SGLT1 protein was decreased and that of PEPT1 protein was increased [24].
• To examine whether SGLT1 and GLUT2 colocalize to the same tubular epithelial cells in rat kidney, double-immunoperoxidase studies with dual chromogens and paraformaldehyde perfusion-fixed frozen sections of rat kidney were performed [29].

References