A DIRECT ASSAY FOR PROINSULIN IN PLASMA AND ITS APPLICATIONS IN HYPOGLYCAEMIA

A direct radioimmunoassay in unextracted plasma is described. The assay has a sensitivity of 4 pmol/l (2 standard deviation from zero). The proinsulin antiserum was immuno‐adsorbed against human C‐peptide and insulin coupled to glass beads. Cross‐reactivity of the antiserum was assessed and shown to be less than 0·01% with both peptides. In normal healthy fasting subjects the plasma proinsulin level was 6·7 ± 1·7 pmol/l (n=17) (mean ± SD). Fasting proinsulin levels in non‐insulin dependent diabetics were significantly elevated compared with non diabetics (14·2 ± 2 pmol/l (n=11) vs 6·7 ± 1·7 (n=17) P>0·005). The insulin/proinsulin ratio was 3·4:1 in the non‐insulin dependent diabetic compared with 6:1 in non‐diabetics. Samples from 21 insulinoma patients were assayed and mean fasting plasma proinsulin level was 255 pmol/l ± 479 when the patients were hypoglycaemic. The range in pro‐insulin levels was large (30–2300 pmol/l). Mean fasting proinsulin level in three hypoglycaemic subjects due to sulphonylurea overdose was 15·7 ± 2·3 pmol/l. The molar ratio of proinsulin to insulin was 1:6 in healthy subjects, 1:1 in insulinoma patients and 10:1 in sulphonylurea induced hypoglycaemic patients.

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