Disruption of aldose reductase gene (Akr1b1) causes defect in urinary concentrating ability and divalent cation homeostasis

Aldose reductase (AKR1B1) is the first enzyme in the polyol pathway through which glucose is converted to sorbitol, and has been implicated in the eti ology of diabetic complications. However, its physiological role is still n ot well understood. In the kidney, AKR1B1 is quite abundant in the collecti ng tubule cells and thought to provide protection against hypertonic enviro nment. We report here that the mice lacking AKR1B1 showed hypercalcemia, hy percalcemia, hypermagnesemia, and reduced ability to concentrate urine, sug gesting a new physiological role of AKR1B1 in divalent cation homeostasis. (C) 2000 Academic Press.