Mechanism for sodium retention by insulin plus glucose in diabetes may involve renal epithelial sodium channels (ENaC)

This study tested the role of epithelial sodium channels (ENaC) in the sodium‐retaining effect of insulin we have reported in diabetic dogs. Alloxan‐treated dogs (n=3) were maintained normoglycemic using i.v. insulin replacement. Following control, insulin replacement was stopped to begin an 8‐day diabetic period. In 2 dogs, insulin was infused 24 hr/day into the renal artery (ir.) during diabetes. Consistent with our previous results, diabetes caused sustained natriuresis in the control diabetic dog, with UNaV equaling 93 mEq/day on day 6 of diabetes vs. an average of only 52 mEq/day in the 2 diabetic dogs with ir. insulin. Amiloride (iv.) was administered in all dogs on diabetes days 7 and 8 and raised UNaV in both groups to similar levels (165 and 132 mEq/day in control and i.r. insulin dogs, respectively). In a second experiment, diabetes was induced again in all dogs, but amiloride was given during the first 2 days of diabetes. In the control diabetic dog, UNaV increased from 67 mEq/day to 199 and 111 mEq/day on days 1 and 2 of diabetes, respectively. In the 2 dogs with ir. insulin infusion, UNaV increased similarly, from an average of 70 mEq/day to 216 and 86 mEq/day on days 1 and 2 of diabetes. The elimination of the difference in diabetes‐induced natriuresis in control vs. ir. insulin‐infused dogs by amiloride suggests that ENaC contributes significantly to the sodium retaining action of insulin+glucose in diabetes.