Oxyntomodulin: a potential hormone from the distal gut. Pharmacokinetics and effects on gastric acid and insulin secretion in man

Abstract

Abstract Synthetic oxyntomodulin, a predicted product of the glucagon gene, which is produced in the human lower intestinal mucosa, was infused in doses of 100 and 400 ng kg ‐1 h ‐1 into six volunteers to study its pharmacokinetics and effects on pentagastrin‐stimulated gastric acid secretion (100 ng kg ‐1 h ‐1 ). The concentration of oxyntomodulin in plasma measured with a cross‐reacting glucagon assay increased from 37 ± 5 to 106 ± 17 and 301 ± 40 pmol l ‐1 , respectively. The metabolic clearance rate was 5·2 ± 0·7 ml kg ‐1 min ‐1 and the half‐life in plasma was 12 ± 1 min. Oxyntomodulin reduced the pentagastrin‐stimulated acid secretion by 20 ± 9% during the low‐rate infusion ( P < 0·05) and by 76 ± 10% during the high‐rate infusion ( P < 0·05). In accordance with the homology with glucagon, there was a small, significant rise in plasma concentrations of insulin and insulin C‐peptide during oxyntomodulin infusion. Oxyntomodulin may therefore be included among the potential incretins and enterogastrones in man.