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

The liver manufactures albumin at a massive rate and decreases production in times of environmental, nutritional, toxic and trauma stress. Osmotic pressure is a basic evolutionary regulatory factor, and hormonal control over albumin production has been demonstrated. Where and why new or old albumin is degraded are questions which have not been clarified, although the vascular endothelium may well be the degradative site. Albumin is important as a transport protein, as a measure of evolution and as a model to study secretion following synthesis without the intervening steps of glycosylation. Investigations as to how this protein enters the endoplasmic membrane may well answer some of the questions concerning signal peptide insertion (288). The role of the urea cycle intermediate ornithine and its participation in polyamine synthesis, which has a positive effect on albumin synthesis, is under study. Likewise, the inverse relation between acute-phase protein synthesis and albumin synthesis regulated by interleukin 1 and other cytokines will merit further study. These are a few of the concepts which will be tested in the future.

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