1. Jae Young Seong
    1. Graduate School of Medicine, Korea University, Seoul 136-705, Republic of Korea
    1. Correspondence should be addressed to J Y Seong; Email: jyseong{at}


    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.

    • Revision received 16 October 2013
    • Accepted 10 December 2013
    • Made available online as an Accepted Preprint 5 March 2014
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