Abnormal renal glucose handling in X-linked hypophosphataemic mice

1. The renal handling of glucose was determined in male X-linked hypophosphataemic (Hyp/Y) mice and in control littermates (+/Y) aged 4 months. Plasma glucose concentration and urinary glucose excretion were measured before and during stepwise increase in glycaemia induced by an acute infusion of glucose. The relationship between plasma glucose concentration and urinary glucose excretion was monitored per ml of glomerular filtrate in mice fed high and low phosphate diets. 2. Hyp/Y mice fed the high phosphate diet showed a significantly higher glucosuria compared with +/Y littermates. When glycaemia was increased, Hyp/Y mice developed frank glucosuria earlier than +/Y animals. In Hyp/Y mice we could not find a threshold below which virtually no glucose was excreted in the urine, whereas this was clearly visible in +/Y mice. These differences persisted in animals fed the low phosphate diet. 3. Using the acute response to the glucoregulatory hormones, glucagon and insulin, administered exogenously, we found that the regulation of plasma glucose concentration did not differ between Hyp/Y and +/Y mice. 4. The significantly lower plasma glucose concentration observed in Hyp/Y as compared with +/Y mice decreased further during fasting. 5. We conclude that the renal reabsorptive capacity for glucose is defective in Hyp/Y mice and their low plasma glucose concentration may be explained by the renal leak. Therefore the X-linked phosphataemic mouse appears not only to be characterized by a defect in renal phosphate and calcium reabsorption but also by an altered glucose reabsorption.