Cloning and functional expression of the human glucagon-like peptide-1 (GLP-1) receptor

Endocrinology. 1993 Oct;133(4):1907-10. doi: 10.1210/endo.133.4.8404634.


Truncated forms of glucagon-like peptide-1 are the most potent endogenous stimuli of insulin secretion and have powerful antidiabetogenic effects. To determine the structure and coupling mechanisms of the human GLP-1 receptor we have isolated two pancreatic islet cDNAs, encoding the 463 amino acid receptor and differing mainly in their 3' untranslated regions. The deduced amino acid sequence is 90% homologous with the rat GLP-1 receptor. Northern blot analysis shows expression of a single 2.7 kb transcript in pancreatic tissue. When expressed in COS-7 cells the recombinant receptor conferred specific, high affinity GLP-1(7-37) binding. GLP-1(7-37) increased intracellular cAMP in a concentration dependent manner and caused an increase in the free cytosolic calcium ([Ca2+]i) from an intracellular pool, characteristic of phospholipase C (PLC) activation. Thus, like the structurally related glucagon and parathyroid hormone receptors, the human GLP-1 receptor can activate multiple intracellular signaling pathways including adenylyl cyclase and PLC. Knowledge of the GLP-1 receptor structure will facilitate the development of receptor agonists and elucidation of the important role of GLP-1 in normal physiology and disease states.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding, Competitive
  • Blotting, Northern
  • Calcium / metabolism
  • Cell Line, Transformed
  • Cloning, Molecular*
  • Cyclic AMP / metabolism
  • DNA, Complementary / genetics
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Intracellular Membranes / metabolism
  • Molecular Probes / genetics
  • Molecular Sequence Data
  • Receptors, Cell Surface / classification
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism*
  • Receptors, Glucagon*
  • Second Messenger Systems
  • Tissue Distribution


  • DNA, Complementary
  • GLP1R protein, human
  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Molecular Probes
  • Receptors, Cell Surface
  • Receptors, Glucagon
  • Cyclic AMP
  • Calcium

Associated data

  • GENBANK/L09679
  • GENBANK/L09680
  • GENBANK/L09681
  • GENBANK/L09682
  • GENBANK/L09683
  • GENBANK/L16554
  • GENBANK/L16555
  • GENBANK/L16556
  • GENBANK/U01156
  • GENBANK/U01157