Luminal glucose (G)-induced activation of intestinal phosphate (Pi) uptakes involves glucoseo6-phosphate (G6Pase) and AMP-Kinase (AMPK).

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]