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Clearance of Porcine Insulin, Proinsulin, and Connecting Peptide by the Isolated Rat Liver 1

Summary In the isolated rat liver perfusion system, the immunological half-life of crystalline single-component insulin was 17 min. In contrast, there was no significant clearance of either proinsulin or the connecting peptide that links the A and B chain of insulin in the proinsulin molecule. There was also no evidence of conversion of proinsulin to insulin. This may, in part, explain the prolonged in vivo half-life of proinsulin relative to insulin. The authors are most grateful to Dr. M. A. Root (Lilly) for the proinsulin antibody, and to Dr. R. E. Chance (Lilly) for the purified proinsulin, connecting peptide, and single-component insulin used in this study. We also appreciate the excellent technical assistance of Mrs. Carla Gullickson, Miss Ellen Laschansky, and Mrs. Jeanette Teague.