Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter

Abstract

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.

GLUT2 and the incretin receptors are involved in glucose-induced incretin secretion

“…GLUT-2 is expressed in the CNS (Leloup et al, 1994) and required for ANSmediated hepatoportal glucose sensing (Burcelin et al, 2000b). However, glucose enters the epithelial cell through the sodium-glucose cotransporter SGLT-1 (Turk et al, 1991) and is released into the mesenteric blood through GLUT2. We could suggest that the GLUT2-dependent enteric glucose absorption is not a major regulatory mechanism for enteric glucose sensing.…”

Tight junction-based epithelial microenvironment and cell proliferation

“…Thus, the TJ physiology should be an important contributor to the epithelial and endothelial physiology. As an example, it is well known that paracellular ionic permeability dominates the transcellular ionic permeability in the small intestine (Frizzell and Schultz, 1972;Okada et al, 1977), and has an important function in the intestinal physiology, such as in the absorption of nutrients (Hopfer, 1977;Turk et al, 1991). Similarly, re-absorption of ions through paracellular pathways in the kidney is very important for regulating the ionic homeostasis of the body (Simon et al, 1999).…”

Molecular Analysis of the SGLT2 Gene in Patients with Renal Glucosuria

“…The molecular bases of three congenital defects of cellular glucose transport, affecting either facilitative ("passive") or sodium-dependent ("active") transport, have been elucidated in recent years (1)(2)(3). In addition, a defect of the renal lowaffinity sodium/glucose cotransporter SGLT2 gene (also referred to as SLC5A2, [OMIM 182381]) has long been proposed to cause renal glucosuria (OMIM 233100) (4).…”