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.

Vanadate but not tungstate prevents the fructose-induced increase in GLUT5 expression and fructose uptake by neonatal rat intestine.

Intermediary signals, precociously enhancing GLUT5 transcription in response to perfusion of its substrate, fructose, in the small intestine of neonatal rats, are not known. Because glucose-6-phosphatase (G6Pase), glucose-6-phosphate translocase (G6PT), and fructose-1,6-bisphosphatase (FBPase) expression increases parallel to or precedes that of GLUT5, we investigated the link between these gluconeogenic genes and GLUT5 by using vanadate or tungstate, potent inhibitors of gluconeogenesis. Small intestinal perfusions of 20-d-old rats were performed with fructose alone, fructose + vanadate or tungstate, glucose alone, and glucose + vanadate or tungstate.

Fructose-induced increases in neonatal rat intestinal fructose transport involve the PI3-kinase/Akt signaling pathway.

Expression of rat glucose transporter-5 (GLUT5) is tightly regulated during development. Expression and activity are low throughout the suckling and weaning stages, but perfusion of the small intestinal lumen with fructose solutions during weaning precociously enhances GLUT5 activity and expression. Little is known, however, about the signal transduction pathways involved in the substrate-induced precocious GLUT5 development.

Cyclic AMP stimulates fructose transport in neonatal rat small intestine.

Intestinal fructose transporter (GLUT5) expression normally increases significantly after completion of weaning in neonatal rats. Increases in GLUT5 mRNA, protein, and activity can be induced in early weaning pups by precocious consumption of dietary fructose or by perfusion of the small intestine with fructose solutions. Little is known about the signal transduction pathway of the dietary fructose-mediated increase in GLUT5 expression during early intestinal development.

Fructose-responsive genes in the small intestine of neonatal rats.

The intestinal brush border fructose transporter GLUT5 (SLC2A5) typically appears in rats after weaning is completed. However, precocious consumption of dietary fructose or in vivo perfusion for 4 h of the small intestine with high fructose (HF) specifically stimulates de novo synthesis of GLUT5 mRNA and protein before weaning is completed. Intermediary signals linking the substrate, fructose, to GLUT5 transcription are not known but should also respond to fructose perfusion.

Regulation of rat intestinal GLUT2 mRNA abundance by luminal and systemic factors.

Fructose in the lumen of the small intestine is transported across the brush border membrane by GLUT5, then across the basolateral membrane by GLUT2, which also transports glucose. Diets containing high fructose (HF) specifically enhance intestinal GLUT5 expression in neonatal rats, but there is little information concerning the dietary regulation of GLUT2 expression during early development. In this study, we perfused for 1-4 h 100 mM fructose, glucose (HG), alpha-methylglucose, or mannitol solutions into the jejunum of anaesthetized 20-day-old rat pups.