Dexamethasone sensitizes the neonatal intestine to fructose induction of intestinal fructose transporter (Slc2A5) function.
The recent dramatic increase in fructose consumption is tightly correlated with an equally dramatic surge in the incidence of type 2 diabetes and obesity in children, but little is known about dietary fructose metabolism and absorption in neonates. The expression of the rat intestinal fructose transporter GLUT5 [Slc2A5, a member of the glucose transporter family (GLUT)] can be specifically induced by its substrate fructose, but only after weaning begins at 14 d of age. In suckling rats younger than 14 d old, dietary fructose cannot enhance GLUT5 expression. The aim of this study was to identify the mechanisms allowing fructose to stimulate GLUT5 during weaning. After intestines were perfused with fructose or glucose (control), using microarray hybridization we showed that of 5K genes analyzed in 10-d-old pups, only 13 were fructose responsive. Previous work found approximately 50 fructose-responsive genes in 20-d-old pups. To identify fructose-responsive genes whose expression also changed with age, intestines of 10- and 20-d-old littermate pups perfused with fructose were compared by microarray. Intestines of 10- and 20-d-old pups perfused with glucose were used to segregate age- but not fructose-responsive genes. About 28 genes were up- and 22 down-regulated in 20- relative to 10-d-old pups, under conditions of fructose perfusion, and many were found, by cluster analysis, to be regulated by corticosterone. When dexamethasone was injected into suckling pups before fructose perfusion, the expression of GLUT5 but not that of the sodium glucose cotransporter (SGLT) 1 and of GLUT2, as well as the uptake of fructose but not of glucose increased dramatically. Thus, dexamethasone, which allows dietary fructose to precociously stimulate intestinal fructose absorption, can mimic the effect of age and modify developmental timing mechanisms regulating GLUT5.
Douard
Veronique
V
Department of Pharmacology and Physiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07101-1709, USA.
Cui
Xue-Lin
XL
Soteropoulos
Patricia
P
Ferraris
Ronaldo P
RP
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D005632:Fructose / Q000378:metabolism / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D051296:Glucose Transporter Type 5 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats
D051296:Glucose Transporter Type 5; C495727:Slc2a5 protein, rat; D005632:Fructose; D003907:Dexamethasone; D005947:Glucose