Oxyntomodulin: a potential hormone from the distal gut. Pharmacokinetics and effects on gastric acid and insulin secretion in man.
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 less than 0.05) and by 76 +/- 10% during the high-rate infusion (P less than 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.
Schjoldager
B T
BT
Institute of Medical Physiology C, Panum Institute, University of Copenhagen, Denmark.
Baldissera
F G
FG
Mortensen
P E
PE
Holst
J J
JJ
Christiansen
J
J
D005744:Gastric Acid / Q000187:drug effects / Q000378:metabolism*; D005768:Gastrointestinal Hormones / Q000493:pharmacokinetics*; D005934:Glucagon / Q000097:blood; D004763:Glucagon-Like Peptides / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D053772:Oxyntomodulin; D010418:Pentagastrin / Q000494:pharmacology; D011863:Radioimmunoassay
D005768:Gastrointestinal Hormones; D007328:Insulin; D053772:Oxyntomodulin; D004763:Glucagon-Like Peptides; D005934:Glucagon; D010418:Pentagastrin