Glucagon-like peptide-1-(9-36) amide is a major metabolite of glucagon-like peptide-1-(7-36) amide after in vivo administration to dogs, and it acts as an antagonist on the pancreatic receptor

Eur J Pharmacol. 1996 Dec 30;318(2-3):429-35. doi: 10.1016/s0014-2999(96)00795-9.


This study assesses the importance of metabolites formed following exogenous administration of glucagon-like peptide-1-(7-36) amide (GLP-1). After subcutaneous (s.c.) administration of GLP-1 to dogs the plasma immunoreactivity of GLP-1 measured by two different radioimmunoassays (RIAs) were higher than that measured by a sandwich enzyme-linked immunosorbent assay (ELISA). This discrepancy was due to the formation of the metabolites GLP-1-(9-36) amide, GLP-1-(7-35) and GLP-1-(7-34). Receptor binding studies using baby hamster kidney cells expressing the human pancreatic GLP-1 receptor showed that the affinity of GLP-1-(9-36) amide, GLP-1-(7-35) and GLP-1-(7-34) was 0.95%, 12% and 2.8%, respectively, of the affinity of GLP-1-(7-36) amide. Furthermore, GLP-1-(9-36) amide was shown to be an antagonist to adenylyl cyclase activity, whereas GLP-1-(7-35) and GLP-1-(7-34) were shown to be agonists. GLP-1-(9-36) amide was shown to be present in vivo in amounts up to 10-fold that of GLP-1-(7-36) amide. Due to its low binding affinity, this antagonistic metabolite does not seem to be able to cause physiological antagonism upon s.c. administration of the peptide.

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • Cricetinae
  • Dogs
  • Enzyme-Linked Immunosorbent Assay
  • Glucagon
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide-1 Receptor
  • Glucagon-Like Peptides
  • Humans
  • Pancreas / drug effects*
  • Peptide Fragments / pharmacokinetics*
  • Radioimmunoassay
  • Receptors, Glucagon / antagonists & inhibitors*


  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Peptide Fragments
  • Receptors, Glucagon
  • glucagon-like peptide 1 (7-36)amide
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon