Recent advances in understanding GLP-1R (glucagon-like peptide-1 receptor) function

Biochem Soc Trans. 2013 Feb 1;41(1):172-9. doi: 10.1042/BST20120236.

Abstract

Type 2 diabetes is a major global health problem and there is ongoing research for new treatments to manage the disease. The GLP-1R (glucagon-like peptide-1 receptor) controls the physiological response to the incretin peptide, GLP-1, and is currently a major target for the development of therapeutics owing to the broad range of potential beneficial effects in Type 2 diabetes. These include promotion of glucose-dependent insulin secretion, increased insulin biosynthesis, preservation of β-cell mass, improved peripheral insulin sensitivity and promotion of weight loss. Despite this, our understanding of GLP-1R function is still limited, with the desired spectrum of GLP-1R-mediated signalling yet to be determined. We review the current understanding of GLP-1R function, in particular, highlighting recent contributions in the field on allosteric modulation, probe-dependence and ligand-directed signal bias and how these behaviours may influence future drug development.

Publication types

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

MeSH terms

  • Allosteric Regulation
  • Amino Acid Sequence
  • Diabetes Mellitus, Type 2 / physiopathology
  • Glucagon-Like Peptide 1 / chemistry
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Incretins / physiology
  • Molecular Mimicry
  • Molecular Sequence Data
  • Receptors, Glucagon / metabolism
  • Receptors, Glucagon / physiology*
  • Sequence Homology, Amino Acid
  • Signal Transduction

Substances

  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Incretins
  • Receptors, Glucagon
  • Glucagon-Like Peptide 1