INSULIN-I131 METABOLISM IN HUMAN SUBJECTS: DEMONSTRATION OF INSULIN BINDING GLOBULIN IN THE CIRCULATION OF INSULIN TREATED SUBJECTS 1

Open Access
Publisher Website
Google Scholar
Abstract
Following intravenous administration of I131 labeled insulin to human subjects the time course of radioactivity in plasma was studied chemically and electrophoretically. During trace labeling of regular crystalline insulin with I131 some of the insulin is altered in an unknown fashion so that small but variable fractions of the radioactive material become bound to the serum proteins. The radioactivity bound to serum proteins disappears from plasma much more slowly than unaltered insulin-I131,so that within a short period of time following intravenous administration most of the protein precipitable radioactivity in plasma is not insulin-I131. During paper electrophoresis of plasma containing insulin-I131, the labeled insulin is adsorbed to the paper at the site of appli-cation, thus permitting separation from plasma protein-bouna radioactivity. The half time of disappearance from plasma of adsorbed radioactivity (insulin-I131) after distribution in body fluids is of the order of 40 minutes which is in good agreement with the rate of degradation of insulin-I131 as estimated from the rate of appearance of nonprecipitable radioactivity in the plasma. In subjects treated with insulin for months to years the disappearance of insulin-I131 from plasma is much slower than in subjects never treated with insulin or treated with insulin for less than 2 to 3 months. It was shown that this persistence of relatively high concentrations of insulin-I131 in the plasma of insulin-treated subjects is due to binding of insulin-1131 by an acquired globulin which satisfies the criteria for antibody. The insulin-"insulin transporting antibody" complex migrates in the front running gamma-globulin region on paper or starch block electrophoresis at pH 7.3 or 8.6. The binding of insulin to circulating globulin in these patients is confirmed by ultracentrifugation studies in which it is observed that insulin-I131 in the serum of insulin-treated subjects sediments with the globulins but in the serum of control subjects sediments at a slower rate than serum albumin.