Abstract

Plasma samples from 14 insulin treated diabetic subjects were subjected to Sephadex gel filtration before and after acid-alcohol extraction. The findings were consistent with the presence of insulin antibodies, which on dissociation, released large amounts of immunoreactive material, eluting in positions consistent with proinsulin-like material (PLM) as well as insulin. Because the percentages of PLM were high (compatible with values seen in patients with islet cell tumors), the sources of this material were investigated. Using a specific human C-peptide assay, it was shown in 6 patients that up to 30% of the PLM was of a human proinsulin, demonstrating residual B-cell function in certain insulin treated diabetics. Since 70% of the PLM bound to antibody was exogenous, studies of the behavior of injected labelled proinsulin were made. The half-time disappearance of labelled proinsulin bound to antibody in 2 subjects was shown to be 31 hours compared with only 1.9 hours for insulin bound to antibody. It is concluded that endogenous and exogenous proinsulin, proinsulin-binding antibody and markedly prolonged turnover time for proinsulin bound to antibody account for the elevations of PLM seen in insulin treated diabetics.

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