GLP-1 (glucagon-like peptide 1) and truncated GLP-1, fragments of human proglucagon, inhibit gastric acid secretion in humans.
Glucagon-like peptide 1 amide (GLP-1 amide), a predicted product of the glucagon gene (proglucagon 72-107-amide), and truncated GLP-1 (proglucagon 78-107-amide), recently isolated from porcine small intestine, were infused in doses of 100 and 400 ng/kg/hr and 12.5 and 50 ng/kg/hr, respectively, into eight volunteers to study pharmacokinetics and effects on pentagastrin-stimulated gastric acid secretion (plateau stimulation with pentagastrin at D50: 100 ng/kg/hr). The concentration of GLP-1 in plasma increased from 64 +/- 12 to 189 +/- 23 and 631 +/- 76 pmol/liter, respectively. The concentration of truncated GLP increased from approximately 7 pmol/liter to 28 +/- 3 pmol/liter during the high rate of infusion. A similar increase was seen in response to a mixed meal in eight normal volunteers. The metabolic clearance rate (MCR) of GLP-1 was 2.2 +/- 0.3 and 2.6 +/- 0.3 ml/kg/min, respectively, and the half-life in plasma was 17 +/- 2 min. The MCR of truncated GLP-1 was 13 +/- 2.8 ml/kg/min and the half-life 11.4 +/- 2.1 min. GLP-1 reduced the pentagastrin-stimulated acid secretion 16 +/- 9% during the low-rate infusion and 23 +/- 12% during the high rate (P less than 0.05). Truncated GLP-1 caused a 36 +/- 3% inhibition during the high infusion rate. Thus truncated GLP-1, a naturally occurring peptide, is a potent inhibitor of acid secretion in man and more so than GLP-1.
Schjoldager
B T
BT
Institute of Medical Physiology C, Panum Institute, Copenhagen, Denmark.
Mortensen
P E
PE
Christiansen
J
J
Orskov
C
C
Holst
J J
JJ
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005934:Glucagon / Q000097:blood / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D010187:Pancreatic Hormones / Q000097:blood / Q000494:pharmacology*; D010418:Pentagastrin; D010446:Peptide Fragments / Q000097:blood / Q000494:pharmacology*; D010455:Peptides / Q000097:blood / Q000494:pharmacology*; D052336:Proglucagon; D011498:Protein Precursors / Q000097:blood / Q000494:pharmacology*; D011863:Radioimmunoassay; D013997:Time Factors
D010187:Pancreatic Hormones; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D052336:Proglucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D010418:Pentagastrin