The Renal Handling of Insulin*

Abstract

The renal handling of insulin was studied by insulin immunoassay in arterial blood, renal venous blood, and urine of fasting patients with normal renal function and in peripheral venous blood and urine of normal subjects and patients with renal disease before and after an oral glucose load. A renal arteriovenous insulin concentration difference of approximately 29% was found and suggests that in normal subjects renal insulin clearance is significantly in excess of glomerular filtration rate. The insulin excreted in the urine of normal individuals at no time exceeded 1.5% of the load filtered at the glomerulus. This contrasts with the finding of a urinary insulin clearance approaching glomerular filtration rate in patients with severely impaired renal tubular function. It is suggested that insulin is normally filtered at the glomerulus and then almost completely reabsorbed or destroyed in the proximal tubule. If reabsorption occurs, as seems more likely, reabsorbed insulin does not return to the renal vein and is presumably utilized in renal metabolism together with insulin taken up directly from the blood. Caution is advised in the use of urinary insulin concentration or excretion as an index of serum insulin level or insulin secretion because a very small and variable proportion of filtered insulin appears in the urine in normal subjects, and major changes in urinary insulin excretion may arise as a result of minor tubular defects.