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. Recent microarray results indicate that key gluconeogenic enzymes modulated by cAMP are markedly upregulated by fructose perfusion; hence, we tested the hypothesis that cAMP plays an important role in regulating intestinal fructose absorption by simultaneously perfusing adenylyl cyclase, phosphodiesterase, or protein kinase A (PKA) inhibitors along with fructose. Intestinal fructose uptake rates increased by 100% in rat pups perfused with 8-bromo-cAMP. Simultaneous fructose and dideoxyadenosine (DDA; inhibitor of adenylyl cyclase) perfusion completely inhibited increases in fructose uptake rate induced by perfusion with fructose alone. Fructose perfusion increased intestinal mucosal cAMP concentrations by 27%, but simultaneous perfusion of fructose and DDA inhibited the fructose-induced increase in cAMP. However, GLUT5 and sodium-glucose cotransporter (SGLT1) mRNA abundance and glucose transport rates were each not significantly affected by 8-bromo-cAMP and DDA. Moreover, simultaneous perfusion of the small intestine with fructose and PKA inhibitor or N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamid. 2HCl, both inhibitors of PKA, did not prevent the fructose-induced increases in GLUT5 mRNA abundance and fructose uptake rate. Cyclic AMP appears to modulate fructose transport without affecting GLUT5 mRNA abundance, and without involving PKA.
Cui
Xue-Lin
XL
Department of Pharmacology and Physiology, UMDNJ-New Jersey Medical School, Newark, NJ 07103-2714, USA.
Ananian
Chris
C
Perez
Edwin
E
Strenger
Aidy
A
Beuve
Annie V
AV
Ferraris
Ronaldo P
RP
D000818:Animals; D000831:Animals, Newborn; D000242:Cyclic AMP / Q000494:pharmacology*; D005260:Female; D005632:Fructose / Q000493:pharmacokinetics* / Q000494:pharmacology; D005947:Glucose / Q000493:pharmacokinetics; D051296:Glucose Transporter Type 5; D007408:Intestinal Absorption / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000502:physiology*; D040081:Protein Array Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D051296:Glucose Transporter Type 5; D009004:Monosaccharide Transport Proteins; D005632:Fructose; D000242:Cyclic AMP; D005947:Glucose