The structure and function of the glucagon-like peptide-1 receptor and its ligands

Br J Pharmacol. 2012 May;166(1):27-41. doi: 10.1111/j.1476-5381.2011.01687.x.


Glucagon-like peptide-1(7-36)amide (GLP-1) is a 30-residue peptide hormone released from intestinal L cells following nutrient consumption. It potentiates the glucose-induced secretion of insulin from pancreatic beta cells, increases insulin expression, inhibits beta-cell apoptosis, promotes beta-cell neogenesis, reduces glucagon secretion, delays gastric emptying, promotes satiety and increases peripheral glucose disposal. These multiple effects have generated a great deal of interest in the discovery of long-lasting agonists of the GLP-1 receptor (GLP-1R) in order to treat type 2 diabetes. This review article summarizes the literature regarding the discovery of GLP-1 and its physiological functions. The structure, function and sequence-activity relationships of the hormone and its natural analogue exendin-4 (Ex4) are reviewed in detail. The current knowledge of the structure of GLP-1R, a Family B GPCR, is summarized and discussed, before its known interactions with the principle peptide ligands are described and summarized. Finally, progress in discovering non-peptide ligands of GLP-1R is reviewed. GLP-1 is clearly an important hormone linking nutrient consumption with blood sugar control, and therefore knowledge of its structure, function and mechanism of action is of great importance.

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / physiopathology
  • Glucagon-Like Peptide 1 / drug effects
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucagon-Like Peptide-1 Receptor
  • Glucose / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Insulin / metabolism
  • Ligands
  • Peptides / metabolism*
  • Protein Conformation
  • Receptors, Glucagon / chemistry
  • Receptors, Glucagon / metabolism*


  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Insulin
  • Ligands
  • Peptides
  • Receptors, Glucagon
  • Glucagon-Like Peptide 1
  • Glucose