Discovery of a Novel Glucagon-like Peptide (GCGL) and Its Receptor (GCGLR) in Chickens: Evidence for the Existence of GCGL and GCGLR Genes in Nonmammalian Vertebrates

Glucagon (GCG), glucagon-related peptides, and their receptors have been reported to play important roles including the regulation of glucose homeostasis, gastrointestinal activity, and food intake in vertebrates. In this study, we identified genes encoding a novel glucagon-like peptide (named GCGL) and its receptor (GCGLR) from adult chicken brain using RACE and/or RT-PCR. GCGL was predicted to encode a peptide of 29 amino acids (cGCGL1–29), which shares high amino acid sequence identity with mammalian and chicken GCG (62–66%). GCGLR is a receptor of 430 amino acids and shares relatively high amino acid sequence identity (53–55%) with the vertebrate GCG receptor (GCGR). Using a pGL3-CRE-luciferase reporter system, we demonstrated that synthetic cGCGL1–29, but not its structurally related peptides, i.e. exendin-4 and GCG, could potently activate GCGLR (EC50: 0.10 nm) expressed in Chinese hamster ovary cells, indicating that GCGLR can function as a GCGL-specific receptor. RT-PCR assay revealed that GCGL ex...