GLP-1 (glucagon-like peptide 1) and truncated GLP-1, fragments of human proglucagon, inhibit gastric acid secretion in humans
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GLP-1 (glucagon-like peptide 1) and truncated GLP-1, fragments of human proglucagon, inhibit gastric acid secretion in humans. / Schjoldager, B T; Mortensen, P E; Christiansen, J; Orskov, C; Holst, J J.
In: Digestive Diseases and Sciences, Vol. 34, No. 5, 05.1989, p. 703-8.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - GLP-1 (glucagon-like peptide 1) and truncated GLP-1, fragments of human proglucagon, inhibit gastric acid secretion in humans
AU - Schjoldager, B T
AU - Mortensen, P E
AU - Christiansen, J
AU - Orskov, C
AU - Holst, J J
PY - 1989/5
Y1 - 1989/5
N2 - 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.
AB - 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.
KW - Adult
KW - Dose-Response Relationship, Drug
KW - Female
KW - Gastric Acid/secretion
KW - Glucagon/blood
KW - Glucagon-Like Peptide 1
KW - Half-Life
KW - Humans
KW - Male
KW - Middle Aged
KW - Pancreatic Hormones/blood
KW - Pentagastrin
KW - Peptide Fragments/blood
KW - Peptides/blood
KW - Proglucagon
KW - Protein Precursors/blood
KW - Radioimmunoassay
KW - Time Factors
M3 - Journal article
C2 - 2714145
VL - 34
SP - 703
EP - 708
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
SN - 0163-2116
IS - 5
ER -
ID: 194816036