Sera from nine diabetic patients treated with commercial insulin contained antibodies which reacted to I-125-bovine proinsulin. These antibodies had two distinct components: anti-insulin antibodies which crossreacted with proinsulin, and antiproinsulin antibodies, which were specific to proinsulin and did not react with insulin (purified, single component). Proinsulin-specific antibodies were detectable by their binding to I-125-bovine proinsulin in sera adsorbed with insulin-phe-sepharose or in sera preincubated with excess insulin.

I-125-bovine pro insulin-reactive antibodies showed species specificity. They reacted weakly with porcine proinsulin and appeared to have no crossreactivity with porcine-C-peptide.

The data suggest that proinsulin-specific antibodies (a) may be induced by the contaminants present in commercial insulin; (b) do not inactivate exogenous insulin and therefore, would not influence directly the daily insulin requirements of diabetic individuals.

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