In the intestine, uptake of dietary glucose is for its majority mediated by SGLT1, and humans with mutations in the SGLT1 gene show glucose/galactose malabsorption.
Effects associated with the loss of SGLT1 on pancreatic islet (cyto) morphology and function were investigated by analyzing islets of a SGLT1 knockout mouse model, that were fed a glucose-deficient, fat-enriched diet (SGLT1<sup>-/-</sup>-GDFE) to circumvent the glucose-galactose malabsorption syndrome.
Loss-of-function mutations in the SGLT1 (sodium/glucose co-transporter-1) gene result in a rare glucose/galactose malabsorption disorder and neonatal death if untreated.
We investigated the molecular mechanisms of genetic variations in SGLT1 that cause glucose-galactose malabsorption (GGM) defects using the crystal structure of vSGLT as a model sugar transporter.
Sequence analysis of the 15 protein-coding exons and the corresponding exon-intron boundaries of SLC5A1 gene revealed four homozygous missense mutations, c.152A>G (p.N51S), c.1231G>A (p.A411T), c.1673G>A (p.R558H), and c.1845C>G (p.H615Q), that co-segregate with the GGM phenotype in all of the affected individuals.
Mutations in SGLT1 are associated with glucose-galactose malabsorption, SGLT2 with familial renal glucosuria (FRG), and GLUT2 with Fanconi-Bickel syndrome.
It also considers congenital defects of sugar metabolism caused by aberrant expression of the SGLT1 in glucose-galactose malabsorption and the SGLT2 in familial renal glycosuria.
Nephrocalcinosis in glucose-galactose malabsorption: nephrocalcinosis and proximal tubular dysfunction in a young infant with a novel mutation of SGLT1.
A missense mutation in the Na(+)/glucose cotransporter gene SGLT1 in a patient with congenital glucose-galactose malabsorption: normal trafficking but inactivation of the mutant protein.
A missense mutation in the Na(+)/glucose cotransporter gene SGLT1 in a patient with congenital glucose-galactose malabsorption: normal trafficking but inactivation of the mutant protein.
Two proband siblings with GGM were previously demonstrated to contain a missense mutation (D28N) in the Na(+)-dependent glucose/galactose cotransporter (SGLT1) that accounts for the defect in sugar absorption.
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.
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.
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.