GLP-1 (glucagon-like peptide 1) and truncated GLP-1, fragments of human proglucagon, inhibit gastric acid secretion in humans

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Abstract
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 D 50:100ng/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.