The binding properties of human insulin (recombinant DNA) and human proinsulin were compared in seven healthy volunteers. Specific cell binding of human proinsulin was significantly lower compared with the human insulin receptor binding with an approximately 100-fold lower average affinity (3.71 mol−1 × 108 for human insulin versus 0.042 mol−1 × 108 for human proinsulin). Native human proinsulin at low concentrations had no significant effect on specific human insulin receptor binding. Only at high hormone concentrations human proinsulin could displace human insulin from the insulin receptor. We conclude that in vivo proinsulin-insulin interactions at the receptor do not possess major clinical relevance.

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