Chronic Intrarenal Insulin Replacement Reverses Diabetes Mellitus–Induced Natriuresis and Diuresis

Abstract

We showed recently that sustained natriuresis in type 1 diabetic dogs was attributed to the decrease in insulin rather than the hyperglycemia alone. The sodium-retaining action of insulin appeared to require hyperglycemia, and it completely reversed the diabetic natriuresis and diuresis. This study tested whether the sodium-retaining effect was attributed to direct intrarenal actions of insulin. Alloxan-treated dogs (D; n=7) were maintained normoglycemic using 24-h/d IV insulin replacement. After control measurements, IV insulin was decreased to begin a 6-day diabetic period. Blood glucose increased from 84±6 mg/dL to an average of 428 mg/dL on days 5 and 6, sodium excretion increased from 74±8 to 98±7 meq/d over the 6 days, and urine volume increased from 1645±83 to 2198±170 mL/d. Dir dogs (n=7) were subjected to the same diabetic regimen, but, in addition, insulin was infused continuously into the renal artery at 0.3 mU/kg per minute during the 6-day period. This did not affect plasma insulin. Blood glucose increased from 94±10 mg/dL to an average of 380 mg/dL on days 5 and 6, but sodium excretion averaged 76±5 and 69±8 meq/d during control and diabetes mellitus, respectively. The diuresis also was prevented. Glomerular filtration rate increased only in Dir dogs, and there was no change in mean arterial pressure in either group. This intrarenal insulin infusion had no effect on sodium or volume excretion in normal dogs. Intrarenal insulin replacement in diabetic dogs caused a sustained increase in tubular reabsorption that completely reversed diabetic natriuresis. Insulin plus glucose may work to prevent salt wasting in uncontrolled type 2 diabetes mellitus.