Signal transduction of the GLP-1-receptor cloned from a human insulinoma

FEBS Lett. 1994 Jul 4;348(1):7-13. doi: 10.1016/0014-5793(94)00553-2.


GLP-1 (glucagon-like peptide 1 (7-36) amide) plays an important role in the regulation of insulin secretion and proinsulin gene expression of pancreatic beta-cells. Patients with insulinoma tumors show uncontrolled insulin hypersecretion. This study demonstrates the molecular cloning of a cDNA for the GLP-1 receptor from a human insulinoma employing a lambda-gt11 cDNA library. The cloned cDNA encoded a seven transmembrane domain protein of 463 amino acids which showed high homology to the GLP-1 receptor in normal human pancreas. Four amino acid exchanges were found in comparison to a receptor sequence obtained from regular pancreatic islets. When transfected transiently into COS-7 or stably into fibroblast CHL cells a high affinity receptor was expressed which coupled to the adenylate cyclase with normal basal cAMP and increasing intracellular cAMP levels under GLP-1 stimulation. The receptor accepted GLP-1 and the non-mammalian agonist exendin-4 as high affinity ligands. In transfected COS-7 cells, GLP-1 did not influence intracellular calcium, whereas in the stably transfected fibroblasts GLP-1 transiently increased intracellular calcium to a small extent. The understanding of GLP-1 receptor regulation and signal transduction will aid in the discovery of compounds that act as agonists of the GLP-1 receptor for potential use in the treatment of diabetes and will facilitate the understanding of its expression under normal and pathophysiological conditions.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Northern
  • Calcium / metabolism
  • Cell Line
  • Cloning, Molecular
  • Cyclic AMP / metabolism
  • Glucagon*
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptides
  • Humans
  • Insulinoma / metabolism
  • Molecular Sequence Data
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism*
  • RNA / isolation & purification
  • Rats
  • Receptors, Glucagon / genetics
  • Receptors, Glucagon / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • Transfection


  • Peptide Fragments
  • Receptors, Glucagon
  • Recombinant Proteins
  • glucagon-like peptide 1 (7-36)amide
  • Glucagon-Like Peptides
  • RNA
  • Glucagon-Like Peptide 1
  • Glucagon
  • Cyclic AMP
  • Calcium