human proinsulin

Human proinsulin is the single-chain protein precursor to insulin, consisting of the A and B chains connected by a C-peptide. In the 1980s, Eli Lilly developed biosynthetic human proinsulin (LY127339) using recombinant DNA technology as a potential long-acting therapy for diabetes mellitus. It was hypothesized that its longer plasma half-life and slower clearance compared to regular insulin would provide a more stable basal insulin effect. However, clinical development was halted in the late 1980s after Phase 3 trials revealed an unexpectedly high incidence of myocardial infarction in patients treated with proinsulin compared to those on standard insulin regimens. While it acts as an agonist at the insulin receptor, its affinity is significantly lower than that of mature insulin, and it may have disproportionate effects on hepatic versus peripheral tissues.

Other names

proinsulinbiosynthetic human proinsulinBHPI