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

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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.