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. As expected, fructose, but not glucose nor glucose + inhibitor perfusion, increased GLUT5 mRNA abundance and fructose transport. Fructose perfusion dramatically increased G6Pase mRNA abundance but had no effect on G6Pase activity. In sharp contrast, fructose perfusion did not increase FBPase gene expression but stimulated FBPase activity. Both vanadate and tungstate significantly inhibited G6Pase activity but did not prevent the fructose-induced increases in G6Pase and G6PT gene expression. Perfusion with fructose + vanadate prevented the fructose-induced increases in fructose transport and GLUT5 mRNA abundance, whereas perfusion with fructose + tungstate did not. Interestingly, vanadate, but not tungstate, inhibited the fructose-induced increase in FBPase activity. Thus, vanadate inhibition of fructose-induced increases in FBPase activity paralleled exactly vanadate inhibition of fructose-induced increases in GLUT5 mRNA abundance and activity. Fructose-induced changes in FBPase activity may regulate changes in GLUT5 expression and activity in the small intestine of neonatal rats. The marked increases in intestinal G6Pase and GLUT5 mRNA abundance may be a parallel response to different factors released during fructose perfusion.
Kirchner
Séverine
S
Department of Pharmacology and Physiology, University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School, Newark, NJ 07103-2714, USA.
Kwon
Edward
E
Muduli
Anjali
A
Cerqueira
Carla
C
Cui
Xue-Lin
XL
Ferraris
Ronaldo P
RP
D000818:Animals; D000831:Animals, Newborn; D017920:Antiporters / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005632:Fructose / Q000008:administration & dosage* / Q000378:metabolism; D006597:Fructose-Bisphosphatase / Q000037:antagonists & inhibitors / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage; D051296:Glucose Transporter Type 5 / Q000235:genetics*; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000737:chemistry / Q000201:enzymology; D007422:Intestines / Q000187:drug effects; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017973:Tungsten Compounds / Q000008:administration & dosage*; D014638:Vanadates / Q000008:administration & dosage*
D017920:Antiporters; D004791:Enzyme Inhibitors; D051296:Glucose Transporter Type 5; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C503533:Slc37a4 protein, rat; D017973:Tungsten Compounds; D005632:Fructose; D014638:Vanadates; D006597:Fructose-Bisphosphatase; D005952:Glucose-6-Phosphatase; D005947:Glucose; C045951:tungstate