Molecular evolution of GPCRs: GLP1/GLP1 receptors.

Abstract:

:Glucagon-like peptide 1 (GLP1) is an intestinal incretin that regulates glucose homeostasis through stimulation of insulin secretion from pancreatic β-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.

journal_name

J Mol Endocrinol

authors

Hwang JI,Yun S,Moon MJ,Park CR,Seong JY

doi

10.1530/JME-13-0137

subject

Has Abstract

pub_date

2014-06-01 00:00:00

pages

T15-27

issue

3

eissn

0952-5041

issn

1479-6813

pii

JME-13-0137

journal_volume

52

pub_type

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