125I-insulin metabolism by rat liver cells: preferential binding and degradation of insulin labeled at TyrA14.

The binding and degradation of highly purified A14-[125I]monoiodoinsulin and A19-[125I]monoiodoinsulin were compared in isolated rat hepatocytes. A14-125I-insulin was bound more rapidly and was degraded more rapidly than was A19-125I-insulin. The difference in the rate of degradation between the two preparations was apparent when either tricholoroacetic acid precipitation or binding to specific insulin receptors on cultured human lymphocytes was used for assay. These results provide evidence that binding to its receptor is the first step in insulin degradation by liver cells.