Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucose/galactose malabsorption (GGM) is an autosomal recessive disease manifesting within the first weeks of life and characterized by a selective failure to absorb dietary glucose and galactose from the intestine. The consequent severe diarrhoea and dehydration are usually fatal unless these sugars are eliminated from the diet. Intestinal biopsies of GGM patients have revealed a specific defect in Na(+)-dependent absorption of glucose in the brush border. Normal glucose absorption is mediated by the Na+/glucose cotransporter in the brush border membrane of the intestinal epithelium. Cellular influx is driven by the transmembrane Na+ electrochemical potential gradient; thereafter the sugar moves to the blood across the basolateral membrane via the facilitated glucose carrier. We have previously cloned and sequenced a Na+/glucose cotransporter from normal human ileum and shown that this gene, SGLT1, resides on the distal q arm of chromosome 22. We have now amplified SGLT1 complementary DNA and genomic DNA from members of a family affected with GGM by the polymerase chain reaction. Sequence analysis of the amplified products has revealed a single missense mutation in SGLT1 which cosegregates with the GGM phenotype and results in a complete loss of Na(+)-dependent glucose transport in Xenopus oocytes injected with this complementary RNA.
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PMID:Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter. 200 13

Intestinal uptake of dietary glucose and galactose is mediated by the SGLT1 Na+/glucose cotransporter of the brush border. An SGLT1 missense mutation underlies hereditary glucose/galactose malabsorption, characterized by potentially fatal diarrhea; conversely, oral rehydration therapy exploits normal transport to alleviate life-threatening diarrhea of infectious origin. We have mapped the entire human SGLT1 Na+/glucose cotransporter gene from cosmid and lambda phage clones representing a genomic region of 112 kilobases. Transcription initiation occurred from a site 27 base pairs 3' of a TATAA sequence. All exon-flanking regions were sequenced, and the entire 112-kilobase region mapped with four restriction enzymes. SGLT1 is comprised of 15 exons (spanning 72 kilobases); a possible evolutionary origin from a six-membrane-span ancestral precursor via a gene duplication event is suggested from comparison of exons against protein secondary structure and from sequence considerations. A new missense mutation in exon 1 causing glucose/galactose malabsorption is also described. This is the first Na(+)-dependent cotransporter gene structure reported. These data facilitate the search for new glucose/galactose malabsorption-related mutations in this important gene and provide a basis for future evolutionary comparisons with other Na(+)-dependent cotransporters.
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PMID:Structure of the human Na+/glucose cotransporter gene SGLT1. 819 56

The Na+/glucose cotransporter gene SGLT1 encodes the primary carrier protein responsible for the uptake of the dietary sugars glucose and galactose from the intestinal lumen. SGLT1 transport activity is currently exploited in oral rehydration therapy. The 75-kDa glycoprotein is localized in the brush border of the intestinal epithelium and is predicted to comprise 12 membrane spans. In two patients with the autosomal recessive disease glucose/galactose malabsorption, the underlying cause was found to be a missense mutation in SGLT1, and the Asp28-->Asn change was demonstrated in vitro to eliminate SGLT1 transport activity. The SGLT1 gene was previously shown to reside on the distal q arm of chromosome 22 (11.2-->qter). We have used a cosmid probe for fluorescence in situ hybridization, which refines the localization to 22q13.1, and provide an example of the utility of the SGLT1 probe as a diagnostic for genetic diseases associated with translocations of chromosome 22.
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PMID:Assignment of the human Na+/glucose cotransporter gene SGLT1 to chromosome 22q13.1. 824 93

Cotransporters harness ion gradients to drive 'active' transport of substrates into cells, for example, the Na+/glucose cotransporter (SGLT1) couples sugar transport to Na+ gradients across the intestinal brush border. Glucose-Galactose Malabsorption (GGM) is caused by a defect in SGLT1. The phenotype is neonatal onset of diarrhea that results in death unless these sugars are removed from the diet. Previously we showed that two sisters with GGM had a missense mutation in the SGLT1 gene. The gene has now been screened in 30 new patients, and a heterologous expression system has been used to link the mutations to the phenotype.
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PMID:Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactose malabsorption. 856 65

Dietary sugars are transported from the intestinal lumen into absorptive enterocytes by the sodium-dependent glucose transporter isoform 1 (SGLT1). Regulation of this protein is important for the provision of glucose to the body and avoidance of intestinal malabsorption. Although expression of SGLT1 is regulated by luminal monosaccharides, the luminal glucose sensor mediating this process was unknown. Here, we show that the sweet taste receptor subunit T1R3 and the taste G protein gustducin, expressed in enteroendocrine cells, underlie intestinal sugar sensing and regulation of SGLT1 mRNA and protein. Dietary sugar and artificial sweeteners increased SGLT1 mRNA and protein expression, and glucose absorptive capacity in wild-type mice, but not in knockout mice lacking T1R3 or alpha-gustducin. Artificial sweeteners, acting on sweet taste receptors expressed on enteroendocrine GLUTag cells, stimulated secretion of gut hormones implicated in SGLT1 up-regulation. Gut-expressed taste signaling elements involved in regulating SGLT1 expression could provide novel therapeutic targets for modulating the gut's capacity to absorb sugars, with implications for the prevention and/or treatment of malabsorption syndromes and diet-related disorders including diabetes and obesity.
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PMID:T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. 1785 58