[Determination of plasma proinsulins, insulin and C-peptide]

Insulin is synthesized from a precursor, proinsulin, then converted in the beta cell by sequential limited proteolysis into insulin and C-peptide, which are stored in secretory granules derived from the Golgi apparatus. Since this process is incomplete, some intact and partially processed proinsulins (split proinsulins) remain trapped in the granules and enter the circulation with insulin and C-peptide. As proinsulins are present in low concentration in serum and show structural homology with insulin and C-peptide, only two-site immunoassays using monoclonal antibodies can achieve sensitive and specific measurements of their intact and split forms. Insulin radioimmunoassays using polyclonal antibodies are not specific since such antibodies cross-react with proinsulins. Two-site immunoassays using monoclonal antibodies improve the specificity and the sensitivity of insulin determination. C-Peptide concentration is measured by radioimmunoassays using polyclonal antibodies which cross-react with proinsulins.