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Amidated and non-amidated glucagon-like peptide-1 (GLP-1): non-pancreatic effects (cephalic phase acid secretion) and stability in plasma in humans

Regulatory Peptides
Publication Date
DOI: 10.1016/s0167-0115(98)00044-5
  • Sham Feeding
  • Proglucagon-Derived Peptides
  • Carboxyamidation
  • Enterogastrone
  • Peptide Metabolism
  • Biology
  • Medicine
  • Pharmacology


Abstract The incretin and enterogastrone hormone, GLP-1, occurs in an amidated (GLP-1 (7–36) amide; 75%) and a glycine-extended (GLP-1 (7–37); 25%) form. Their effects on the endocrine pancreas are similar and their overall (mainly renal) elimination rates appear to equal. Assuming that they might differentially affect non-pancreatic targets we investigated the effect of GLP-1 (7–37) infused at 0.7 pmol/kg/min on sham-feeding induced acid secretion in six healthy volunteers. The infusion increased the plasma concentrations from 16±2 pmol/l to 45±2 pmol/l. This was associated with a 61±14% decrease in acid output compared to saline and was not significantly different from that previously observed with GLP-1 (7–36) amide infused at the same rate. We then compared the degradation of the two forms in human plasma at 37°C in vitro. T 1/2 values were 32±3 (7–37) and 42±2 min (7–36) amide ( P=0.007). The difference in metabolism persisted after addition of diprotin A, an inhibitor of dipeptidyl peptidase IV, the enzyme responsible for the initial degradation of GLP-1 in plasma, and broader enzyme inhibitors. Thus, the only effect of the amidation of GLP-1 seems to be to enhance its survival in plasma.

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