Metabolism of single-component and high-molecular-weight radioactive insulin in rats.

Single component (125I)iodoinsulin injected in rats was converted into a high-molecular-weight form. This form of radioactive insulin was shown to be metabolized significantly more slowly and to exhibit a more prolonged half-life than the single-component radioactive insulin. When injected in rats, it remained predominantly in the high-molecular-weight form without conversion into free, single-component insulin. A significant amount of radioactivity was shown to be in the kidneys of rats following the injection of single-component radioactive insulin. The radioactivity of kidney homogenates was shown to exhibiti molecular sizes similar to those of single-component insulin, gamma globulin, and insulin degradation products. The injection of the high-molecular-weight form of radioactive insulin did not produce a significant accumulation of radioactivity in the kidneys of the rats; the radioactivity remained primarily in the blood of the rats, a finding consistent with the observed prolonged half-life of this form of radioactive insulin. The radioactivity in the urine of the animals injected with the single component or the high-molecular-weight radioactive insulin was present only in the region corresponding to degradation products.