GLP-1 (Glucagon-Like Peptide 1) and Truncated GLP-1, Fragments of Human Proglucagon, Inhibit Gastric Acid Secretion in Humans

Dig Dis Sci. 1989 May;34(5):703-8. doi: 10.1007/BF01540341.

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 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dose-Response Relationship, Drug
  • Female
  • Gastric Acid / metabolism*
  • Glucagon / blood
  • Glucagon / pharmacology*
  • Glucagon-Like Peptide 1
  • Half-Life
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Hormones / blood
  • Pancreatic Hormones / pharmacology*
  • Pentagastrin
  • Peptide Fragments / blood
  • Peptide Fragments / pharmacology*
  • Peptides / blood
  • Peptides / pharmacology*
  • Proglucagon
  • Protein Precursors / blood
  • Protein Precursors / pharmacology*
  • Radioimmunoassay
  • Time Factors

Substances

  • Pancreatic Hormones
  • Peptide Fragments
  • Peptides
  • Protein Precursors
  • Proglucagon
  • Glucagon-Like Peptide 1
  • Glucagon
  • Pentagastrin