MOlecular evolution of GPCRs: GLP1/GLP1 receptors

Jong Ik Hwang, Seongsik Yun, Mi Jin Moon, Cho Rong Park, Jae Young Seong

Research output: Contribution to journalReview article

15 Citations (Scopus)

Abstract

Glucagon-like peptide 1 (GLP1) is an intestinal incretin that regulates glucose homeostasis through stimulation of insulin secretion from pancreatic b-cells and inhibits appetite by acting on the brain. Thus, it is a promising therapeutic agent for the treatment of type 2 diabetes mellitus and obesity. Studies using synteny and reconstructed ancestral chromosomes suggest that families for GLP1 and its receptor (GLP1R) have emerged through two rounds (2R) of whole genome duplication and local gene duplications before and after 2R. Exon duplications have also contributed to the expansion of the peptide family members. Specific changes in the amino acid sequence following exon/gene/genome duplications have established distinct yet related peptide and receptor families. These specific changes also confer selective interactions between GLP1 and GLP1R. In this review, we present a possible macro (genome level)- and micro (gene/exon level)-evolution mechanisms of GLP1 and GLP1R, which allows them to acquire selective interactions between this ligand-receptor pair. This information may provide critical insight for the development of potent therapeutic agents targeting GLP1R.

Original languageEnglish
Pages (from-to)T15-T27
JournalJournal of Molecular Endocrinology
Volume52
Issue number3
DOIs
Publication statusPublished - 2014 Mar 5

Keywords

  • Duplication
  • Evolution
  • Exon
  • G protein-coupled receptor
  • GLP1
  • GLP1R
  • Gene
  • Genome

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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