Effect of Iodination on the Biological Activity of Insulin

Abstract

IT has never been possible to prove directly that iodinated insulin molecules and normal insulin molecules are biologically indistinguishable. This is partly because of the heterogeneous nature of iodo-insulin preparations and partly because the notorious insensitivity of insulin bio-assays makes it difficult to detect small losses of biological activity. In view of the increasing use of iodine-131 iodo-insulin as a radioactive tracer for insulin it is important to know that they behave identically. In these experiments the biological activities of various iodine-131 iodo-insulin preparations have been compared with the average number of iodine atoms per insulin molecule. A sudden drop in biological activity has been observed when the degree of iodination exceeds about 3 atoms iodine/mol. By integrating these results with existing knowledge^1,2 on the probable degree of heterogeneity of various iodo-insulin preparations indirect evidence has been obtained that iodine-131 iodo-insulin is a valid tracer for the natural hormone, provided that it is not too heavily iodinated.