The C-peptide of proinsulin: Its diagnostic use and a possible physiological role.

A radioimmunoassay was developed and validated for human C-peptide in unextracted plasma, using a synthetic 31 amino acid human C-peptide for immunogen, standard and tracer. The sensitivity of the assay (10 pg/tube) enabled the measurement of both fasting and stimulated circulating C-peptide levels. Normal ranges were established in lean healthy volunteers after (a) fasting (b) stimulation of insulin secretion using oral and intravenous stimuli (c) suppression of endogenous insulin secretion using exogenous insulin. Human C-peptide measurements were used to investigate patients presenting with hypoglycaemia due to a number of clinical conditions and were found to be of especial use in the differencial diagnosis of the factitious hypoglycaemia of insulin abuse. A rat C-peptide radioimmunoassay was developed and validated to investigate the possibility that C-peptide, as well as insulin, inhibits fat stimulated GIP release. Both exogenous and endogenous C-peptide were shown to inhibit fat stimulated GIP release in rat fed normal laboratory food. However, neither insulin or C-peptide were effective in inhibiting fat stimulated GIP release in rats maintained on shortterm high fat diets. Studies were, therefore, extended to investigate the feed-back inhibition of exogenous insulin on GIP release in humans maintained on low and high fat dietary regimens. Exogenous insulin was found to be ineffective in inhibiting fat stimulated GIP secretion in subjects maintained on a high fat diet. The control of GIP secretion with its consequent effect on insulin secretion via the enteroinsular axis therefore appears to be affected by dietary fat intake