Immunoreactive insulin (IRI), C-peptide, and proinsulin were determined in 46 fasting nondiabetic persons. The means ± S.D. for IRI, C-peptide, and proinsulin (in pmol/ml.) in the 46 nondiabetics were 0.054 ± 0.027, 0.39 ± 0.12, and 0.014 ± 0.009, respectively. The molar ratio between C-peptide and IRI varied from 4.0 to 16.7, with a mean value of 7.9 ± 3.4. Proinsulin constituted 5–36 per cent of IRI, with a mean of 20 ± 10 per cent.

Sera from 24 diabetics aged 17–67 years treated with conventional crystalline insulin for durations of from one to 29 years (mean: 15 years), all of whom had circulating insulin antibodies, were extracted with acid ethanol. Total IRI varied from 2.0 to 22.6 pmol/ml. C-peptide was detectable in only three patients (0.05, 0.08, and 0.15 pmol/ml.). In contrast, human proinsulin was found in all patients and ranged from 0.09 to 9.4 pmol/ml., corresponding to 1 to 45 per cent of total IRI. Species-specific immunoassays for bovine and porcine proinsulin revealed the presence of bovine proinsulin in 23 of the patients (mean 0.36 ± 0.20 pmol/ml.) and porcine proinsulin in eight patients (mean 0.15 ± 0.13 pmol/ml.). Total proinsulin constituted 5 to 64 per cent, mean 22 per cent, of total IRI, while human proinsulin amounted to 1 to 45 per cent, mean 10 per cent, of IRI. Although no insulin secretion could be detected in 21 of the patients, as judged by the amount of C-peptide, the B-cell was still able to secrete proinsulin. Insulin antibodies bind a portion of the secreted proinsulin, thus prolonging its half-life and increasing its concentration in serum.

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