Insulin-I131 Metabolism in Human Subjects: Demonstration of Insulin Binding Globulin in the Circulation of Insulin Treated Subjects 1

Abstract

In recent tracer studies utilizing I131 labeled insulin, in vivo and in vitro metabolic degradation of the labeled insulin has generally been presumed to parallel the disappearance of protein precipitable radioactivity and the appearance of non-precipitable radioactivity (1, 2). The present investigations were prompted by the paucity of data on the metabolic fate of insulin in human subjects and the need for a more specific identification of insulin-I'13 in blood and tissues than has heretofore been employed. The methods developed during this study have permitted quantitative evaluation of the rate of insulin-I'13 metabolism and have led to the discovery of an insulin-transporting globulin in the blood of insulin treated subjects. Regular crystalline insulin 4 was iodinated by the method of Pressman and Eisen (3) (Method A) or by Newerly's modification of their method as previously described (4) (Method B). Insulin-I13. supplied by Abbott Laboratories was also employed in some experiments. The insulin-I.3. solutions prepared in our laboratory were dialyzed against distilled water with frequent changes for 24 to 72 hours, acidified to pH 3.0 with HCl, maintained sterile by the addition of phenol and cultured before use. These lots of insulin-I.3. contained an average of 0.1 to 1.0 iodine atoms per molecule, 12,000 molecular weight, insulin. As deduced from the blood sugar responses in fasting rabbits following intravenous administration of labeled and unlabeled insulin, there was no obvious loss in hypoglycemic potency as a result of the

Immunological and biological properties of iodoinsulin labeled with one or less atoms of iodine per molecule

“…It is not surprising that by recent estimates (26) the half life of unlabeled insulin in man is shorter than by previous estimates with insulin-1311 (27,28). Of particular concern are the studies based on the distribution of insulin-131I in animals (29,30) and tissue (31) which related localization of radioactive insulin to the site at which insulin induces its biological effect.…”

Effects of Ouabain on Insulin Secretion in the Dog

“…Insulin was withheld 24 hours before the experiment, which was performed 3 to 7 days after the surgery. Berson et al (13) showed that injected insulin has a very short half time of disappearance (40 minutes). Davidson et al (14) confirmed this finding in dogs and demonstrated that activity of serum insulin 48 hours after pancreatectomy is not significantly different from zero.…”

New approaches to therapy and diagnosis of diabetes

“…Berson and Yalow [28] reported the presence of circulating insulin-binding immunoglobulins in sera of diabetic patients treated with insulin. It was suggested that insulin resistance and allergies were correlated with the appearance of insulin antibodies.…”