Diabetes Mellitus is a disease characterized by a deficit of or insensitivity to the hormone insulin. Insulin acts on numerous tissues to alter the metabolism of glucose and phosphate, two of the prominent components of energy availability. Diabetes mellitus is associated with disturbances of glucose and phosphate regulatory mechanisms including a loss of phosphate in the urine. Part of this phosphaturia results from a decreased renal reabsorptive capacity for phosphate. We hypothesize that this phosphaturia is due to a decrease in the active transport of phosphate across lumenal brush border membranes (LBBM) of renal cortical proximal tubule cells. In addition to testing this hypothesis we will investigate i) the effects of diabetes on LBBM phosphorylation and the activities of protein kinases and phosphoprotein phosphatases, ii) the relationship between LBBM phosphorylation and Pi transport, iii) the role of parathyroid hormone in diabetic associated defects in LBBM phosphorylation and Pi transport, iv) the inhibition of LBBM Pi transport by glucose and v) the relative contributions of insulin lack and hyperglycemia to diabetic phosphaturia. The basic experimental model to be employed for these studies is the LBBM vesicle isolated from rats with experimentally-induced diabetes. The results should significantly enhance our understanding of diabetes and our knowledge of the mechanism of the renal handling of phosphate.
| Northrup, T E; Garella, S; Perticucci, E et al. (1988) Acidemia alone does not stimulate rat renal Na+-H+ antiporter activity. Am J Physiol 255:F237-43 |
