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More than a century ago, ionizing radiation was observed to damage the radiosensitive small intestine. Although a large number of studies has since shown that radiation reduces rates of intestinal digestion and absorption of nutrients, no study has determined whether radiation affects mRNA expression and dietary regulation of nutrient transporters. Since radiation generates free radicals and disrupts DNA replication, we tested the hypotheses that at doses known to reduce sugar absorption, radiation decreases the mRNA abundance of sugar transporters SGLT1 and GLUT5, prevents substrate regulation of sugar transporter expression, and causes reductions in sugar absorption that can be prevented by consumption of the antioxidant vitamin A, previously shown by us to radioprotect the testes. Mice were acutely irradiated with 137Cs gamma rays at doses of 0, 7, 8.5, or 10 Gy over the whole body. Mice were fed with vitamin A-supplemented diet (100X the control diet) for 5 days prior to irradiation after which the diet was continued until death. Intestinal sugar transport was studied at days 2, 5, 8, and 14 postirradiation. By day 8, o-glucose uptake decreased by ∼10-20% and D-fructose uptake by 25-85%. With increasing radiation dose, the quantity of heterogeneous nuclear RNA increased for both transporters, whereas mRNA levels decreased, paralleling reductions in transport. Enterocytes of mice fed the vitamin A supplement had ⩾ 6-fold retinol concentrations than those of mice fed control diets, confirming considerable intestinal vitamin A uptake. However, vitamin A supplementation had no effect on clinical or transport parameters and afforded no protection against radiation-induced changes in intestinal sugar transport. Radiation markedly reduced GLUTS activity and mRNA abundance, but high-o-fructose diets enhanced GLUTS activity and mRNA expression in both unirradiated and irradiated mice. In conclusion, the effect of radiation may be posttranscriptional, and radiation-damaged intestines can still respond to dietary stimuli. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Nutrient transporters are often specifically and solely regulated by their substrates. However, we recently showed that luminal G-perfusion, but not that of its non-metabolizable analogs or fructose (F), induces Pi uptake in weaning rat. We report here that this activation is mediated by a G-specific induction of both apical sodium-Pi co-transporter (NaPi2b) mRNA and brush-border protein levels. The role of G metabolism was evaluated by modulating the activity of G6Pase, a key enzyme of gluconeogenesis, and AMPK, the main cellular energy sensor. 20 d old rat intestines were perfused with G or F alone, or these sugars plus (1) a G6Pase inhibitor (Tungstate -T- or Vanadate -V-), or (2) an AMPK activator (AICAR) or inhibitor (C75). Perturbing glucose metabolism by inhibiting G6Pase with T or V also inhibits NaPi2b mRNA expression and Pi uptake. AICAR decreases NaPi2b mRNA levels. In contrast, C75 tends to increase NaPi2b gene expression and Pi uptake in both sugar-perfused groups. The effects are specific for NaPi2b since proline or G transporter mRNA levels and activities were not affected. The stimulating effect of G on Pi uptake may be specifically mediated by subsequent G metabolism in the enterocyte. Understanding the mechanisms underlying the potent stimulation of intestinal Pi uptake by G has implications in the management of hyperphosphatemia by dietary carbohydrate. [ABSTRACT FROM AUTHOR]