GLUT2 mutations, translocation, and receptor function in diet sugar managing.
Cloned 20 years ago, GLUT2 is a facilitative glucose transporter in the liver, pancreas, intestine, kidney, and brain. It ensures large bidirectional fluxes of glucose in and out the cell due to its low affinity and high capacity. It also transports other dietary sugars, such as fructose and galactose, within the range of physiological concentrations. Sugars and hormones regulate its gene expression. The contribution of GLUT2 to human metabolic diseases previously appeared modest. However, in the past decade, three major features of the GLUT2 protein have been revealed. First, GLUT2 mutations cause the severe but rare Fanconi-Bickel syndrome, mainly characterized by glycogenosis. Recently, a GLUT2 polymorphism has been associated with preferences for sugary food. Second, the GLUT2 location at the cell surface is regulated; this governs cellular activities dependent on glucose in the intestine and possibly those in the liver and pancreas. For instance, GLUT2 translocation from an intracellular pool to the apical membrane after a sugar meal transiently increases sugar uptake by enterocytes (reviewed in 32). Third, GLUT2 functions as a membrane receptor of sugar. Independently of glucose metabolism, GLUT2 detects the presence of extracellular sugar and transduces a signal to modulate cell functions, including beta-cell insulin secretion, renal reabsorption, and intestinal absorption according to the sugar environment. These recent developments are examined here in heath and metabolic disease, highlighting various unanswered questions.
Leturque
Armelle
A
Centre de recherche des Cordeliers 15 rue de l'école de médecine, F-75006 Paris, France. armelle.leturque@crc.jussieu.fr
Brot-Laroche
Edith
E
Le Gall
Maude
M
D000818:Animals; D050260:Carbohydrate Metabolism; D019422:Dietary Sucrose / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000235:genetics* / Q000378:metabolism*; D006008:Glycogen Storage Disease / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism; D009154:Mutation
D019422:Dietary Sucrose; D051273:Glucose Transporter Type 2