Luminal glucose (G)‐induced activation of intestinal phosphate (Pi) uptakes involves glucose‐6‐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. (NSF‐IBN 235011).