Gluconeogenesis regulates intestinal GLUT5 expression in neonatal rats

Intermediary signals precociously enhancing GLUT5 transcription in response to its substrate fructose are not known. Microarray hybridization identified a cluster of gluconeogenic genes as candidate regulators of GLUT5: glucose‐6‐phosphatase (G6Pase), glucose‐6‐phosphate translocase (G6PT) and fructose‐1,6‐bisphosphatase (FBPase). The fructose‐induced increase in mRNA abundance of G6Pase precedes that of GLUT5. We studied the link between G6Pase and GLUT5 by in vivo inhibition of G6Pase activity with vanadate (V) or tungstate (T). Intestinal perfusions of 20 d old rats were performed with fructose alone, fructose + V or T, glucose alone, and glucose + V or T. Both V and T inhibited G6Pase activity but had no effect on G6Pase and G6PT gene expression. As expected, fructose but not glucose nor glucose + inhibitor perfusion increased GLUT5 mRNA abundance and activity. Intestinal perfusion with fructose + V prevented the fructose‐induced increases in GLUT5 mRNA abundance and activity, whereas perfusion with fructose + T did not. Fructose perfusion dramatically increased G6Pase mRNA abundance but did not affect G6Pase activity. In sharp contrast, fructose perfusion did not affect FBPase expression but stimulated FBPase activity. V but not T inhibited the fructose‐induced increase in FBPase activity. Thus, V inhibition of fructose‐induced increases in FBPase activity paralleled V inhibition of fructose‐induced increases in GLUT5 mRNA abundance and activity. Hence, fructose‐induced changes in FBPase activity may be the key regulator of GLUT5 expression. (NSF‐IBN 0235011; USDA‐NRI 2004‐35206‐14154 & 2003‐35102‐13520)