Disease relevance of SLC5A4

• Transcription of human SAAT1 was demonstrated in various human carcinomas and tumor cell lines [1].

High impact information on SLC5A4

• We have examined the expression and function of a previously undescribed human member (SGLT3/SLC5A4) of the sodium/glucose cotransporter gene family (SLC5) that was first identified by the chromosome 22 genome project [2].
• Functional studies using the Xenopus laevis oocyte expression system showed that hSGLT3 was incapable of sugar transport, even though SGLT3 was efficiently inserted into the plasma membrane [2].
• Transport of beta-D-Glc-IPM and glucose by SAAT1 is apparently performed by the same mechanism because similar sodium dependence, dependence on membrane potential, electrogenicity, and phlorizin inhibition were determined for beta-D-Glc-IPM, D-glucose, and AMG [1].
• Transport of the new chemotherapeutic agent beta-D-glucosylisophosphoramide mustard (D-19575) into tumor cells is mediated by the Na+-D-glucose cotransporter SAAT1 [1].
• A leucine zipper region was detected in both SAAT1 and SGLT1 [3].

Biological context of SLC5A4

• In multiple linear regression, fasting insulin was independently related to total fat within both ethnic groups (model R2 = 0.42 and 0.52 for African Americans and whites, respectively), incremental 30-min insulin to total fat and IAAT in whites only (model R2 = 0.71), and AUC to SAAT in African Americans only (model R2 = 0.49) [4].
• In this substrate specificity study, we examined the interactions of imino sugars with a novel human glucose sensor, sodium/glucose cotransporter type 3 (hSGLT3), using expression in Xenopus laevis oocytes and electrophysiology [5].
• The Na+ Hill coefficient for SGLT3 is approximately 1.5, suggesting low cooperativity between Na+ binding sites [6].
• This finding suggests that hSGLT3, an insulin-independent glucose transporter, is activated with exercise and it may play a significant role in glycemic control with muscle contraction [7].

Anatomical context of SLC5A4

• The message for SAAT1 was a single 2.4-kilobase species in kidney, but mRNA species of 2.4 and 3.7 kilobases were observed in LLC-PK1 cells as well as in intestine [3].
• Expression of SAAT1 in COS-7 cells resulted in increased levels of Na(+)-dependent uptake of 2-(methylamino)isobutyric acid, a specific substrate for the system A amino acid transporter [3].
• African American children had higher insulin concentrations than white children after total body fat, IAAT, and SAAT were controlled for [4].
• We examined the association between the Ala(54)Thr variant in the FABP2 gene and levels of visceral (VAT) and sc (SAAT) abdominal fat in a group of 223 premenopausal African-American (n = 103) and Caucasian (n = 120) women [8].
• Fasting and postchallenge insulin concentrations were determined by oral-glucose-tolerance test, total body fat by dual-energy X-ray absorptiometry, and subcutaneous abdominal (SAAT) and intraabdominal (IAAT) adipose tissue by computerized tomography [4].

Associations of SLC5A4 with chemical compounds

• An important deviation from this trend is potent hSGLT3 activation by the imino sugars 1-deoxynojirimycin (DNJ), N-hydroxylethyl-1-deoxynojirimycin (miglitol), N-butyl-1-deoxynojirimycin (miglustat), N-ethyl-1-deoxynojirimycin, and 1-deoxynojirimycin-1-sulfonic acid, with K0.5 values of 0.5 to 9 microM [5].
• Together these data suggest that detection of glucose in the intestine may involve SGLT-3, possibly expressed by enterochromaffin cells in the intestinal mucosa, and release of 5-HT [9].
• A significant positive correlation of SAAT with total testosterone and serum leptin was found (r = 0.27, p < 0.01, r = 0.64, p < 0.001, respectively) [10].
• Protein expression levels of these transporters were confirmed by immunohistochemistry and Western blotting. hSGLT3 after resistance exercise was found not to be co-localized with the nicotinic acetylcholine receptor [7].

Other interactions of SLC5A4

• Skeletal muscle hSGLT3 and GLUT4 mRNA transcript levels were determined by real time RT-PCR. hSGLT3 transcripts increased by a factor of ten following resistance training compared to control subjects (0.10, P=0.03) [7].

Analytical, diagnostic and therapeutic context of SLC5A4

• Targeting the elevated glucose uptake of tumor cells expressing the SAAT1 glucose transporter, glufosfamide represents an attractive new drug for cancer chemotherapy [11].

References