Effect of myo-inositol on renal Na-K-ATPase in experimental diabetes

Abstract

The activity of Na-K-ATPase in the kidney is increased by experimental diabetes. Because the kidney is rich in myo-inositol and abnormal inositol metabolism has been implicated in early neural complications of diabetes, we studied the effect of myo-inositol supplementation on Na-K-ATPase activity in renal medullary and cortical homogenates of Sprague-Dawley rats made diabetic with streptozotocin. Myo-inositol (650 mg/kg) was administered by gavage daily for 1 and 2 weeks after induction of diabetes. Medullary Na-K-ATPase (μmol/mg protein/h) was increased at 1 week by approximately 60% in diabetic rats versus control (25.9 ± 0.07 v 16.3 ± 0.7; P < .01). This increase was completely prevented by myo-inositol supplementation, despite persistent hyperglycemia. At 2 weeks, similar results were seen; medullary Na-K-ATPase activity was increased by 50% in diabetic rats compared with control, and once again myo-inositol prevented this increase. Sorbinil, the aldose reductase inhibitor, was also administered by gavage (20 mg/kg) for 2 weeks and partially prevented the increase in medullary Na-K-ATPase activity (20.0 ± 0.9; P < .05). At both 7 and 14 days, Na-K-ATPase activity in the cortex of untreated diabetic rats was also significantly increased compared with nondiabetic control rats and the increase was prevented by myo-inositol or Sorbinil. Myo-inositol or Sorbinil did not reduce Na-K-ATPase activity of nondiabetic control rats, nor did they prevent the increase in medullary Na-K-ATPase in compensatory hypertrophy following uninephrectomy. Myo-inositol content of outer medulla was about five to six times that of cortex, but was unaltered by the diabetic state. The effect of myo-inositol supplements on Na-K-ATPase appeared independent of glomerular filtration rate (GFR), since the increase in inulin clearance measured in diabetic rats (0.63 ± 0.05 mL/min/100 g v 0.42 ± 0.04 in controls) was unaffected by myo-inositol. The results indicate that disturbed inositol metabolism may play a role in the renal changes produced by diabetes.