Isolation and Structural Characterization of Proglucagon-Derived Peptides, Pancreatic Polypeptide, and Somatostatin from the UrodeleAmphiuma tridactylum

Cavanaugh, Eleanor; Nielsen, Per F.; Conlon, J. Michael

doi:10.1006/gcen.1996.0003

Cited by 29 publications

(12 citation statements)

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“…xenGLP-1C was most similar to a GLP-1 that was identified in bullfrog (31). The three Xenopus GLP-1-like sequences are equally similar to the GLP-1 sequence from a divergent amphibian lineage, the Amphiuma (32). The GLP-1-like sequence of these peptides raised the possibility that Xenopus GLP-1s may possess incretin-like properties.…”

Section: Discussionmentioning

confidence: 87%

The Xenopus proglucagon gene encodes novel GLP-1-like peptides with insulinotropic properties

Irwin

Satkunarajah

Wen

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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The proglucagon gene encodes several hormones that have key roles in the regulation of metabolism. In particular, glucagon-like peptide (GLP-1), a potent stimulus of insulin secretion, is being developed as a therapy for the treatment of non-insulin-dependent diabetes mellitus. To define structural moieties of the molecule that convey its insulinotropic activity, we have cloned and characterized the proglucagon gene from the amphibian, Xenopus laevis. Unexpectedly, these cDNAs were found to encode three unique glucagon-like-1 peptides, termed xenGLP-1A, xenGLP-1B, and xenGLP-1C in addition to the typical proglucagon-derived hormones glucagon and GLP-2. xenGLP-1A, -1B, and -1C were synthesized and tested for their ability to bind and activate the human GLP-1 receptor (hGLP-1R), and to stimulate insulin release from rat pancreas. All three Xenopus GLP-1-like peptides bind effectively to the hGLP-1R and stimulate cAMP production. Surprisingly, xenGLP-1B(1-30) demonstrated higher affinity for the hGLP-1R than hGLP-1 (IC 50 of 1.1 ؎ 0.4 nM vs. 4.4 ؎ 1.0 nM, respectively, P < 0.02) and was equipotent to hGLP-1 in stimulating cAMP production (EC 50 of 0.17 ؎ 0.02 nM vs. 0.6 ؎ 0.2 nM, respectively, P > 0.05). Further studies demonstrated that hGLP-1, xenGLP-1A, -1B, and -1C stimulate comparable insulin release from the pancreas. These results demonstrate that despite an average of nine amino acid differences between the predicted Xenopus GLPs and hGLP-1, all act as hGLP-1R agonists.

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Section: Discussionmentioning

confidence: 87%

The Xenopus proglucagon gene encodes novel GLP-1-like peptides with insulinotropic properties

Irwin

Satkunarajah

Wen

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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“…Not all frogs studied are recognized to have multiple GLP‐1s, and this may be resultant of alternative splicing of pancreatic or intestinal proglucagon mRNA, or inefficient proteolytic processing 41 . Alternatively, this may be resultant of exon triplication followed by species‐specific exon losses, hence accounting for the different number of GLP‐1s in amphibian species studied 42,43 …”

Section: An Exceptional Case: Fish and Amphibiansmentioning

confidence: 99%

“…41 Alternatively, this may be resultant of exon triplication followed by species-specific exon losses, hence accounting for the different number of GLP-1s in amphibian species studied. 42,43…”

Section: Amphibiansmentioning

confidence: 99%

Insights into the evolution of proglucagon‐derived peptides and receptors in fish and amphibians

Ng¹,

Lee²,

Chow³

2010

Annals of the New York Academy of Sciences

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Glucagon and the glucagon-like peptides (GLP-1 and GLP-2) share a common evolutionary origin and are triplication products of an ancestral glucagon exon. In mammals, a standard scenario is found where only a single proglucagon-derived peptide set exists. However, fish and amphibians have either multiple proglucagon genes or exons that are likely resultant of duplication events. Through phylogenetic analysis and examination of their respective functions, the proglucagon ligand-receptor pairs are believed to have evolved independently before acquiring specificity for one another. This review will provide a comprehensive overview of current knowledge of proglucagon-derived peptides and receptors, with particular focus on fish and amphibian species.

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“…Tetrapod GLP-1 sequences were collected from databases and the literature; Agkistrodon piscivorus (GI:45272441), Amphiuma tridactylum (three-toed salamander), 56 Bufo marinus (giant toad), 21 Ceratophrys ornata (ornate horned frog), 57 Cynops pyrrhogaster (Japanese firebelly newt), 32 Gallus gallus (common chiken), 58 Hoplobatrachus rugulosus (Taiwanese frog), 23 Heloderma Suspectum (Gila monster), 24 Homo sapiens (human), 59 Pyxicephalus adspersus (African bull frog), 60 Pipa pipa (suriname toad), 61 Rana catesbeiana (bull frog), 62 Rana pipiens (northern leopard frog), 22 Xenopus leavis (African clawed frog), 32 Xenopus tropicalis (western clawed frog) (GI:55742076), and H. suspectum exendin-4. 25 Cleavage positions were in most cases determined from sequencing of the peptide itself; otherwise they were transferred from the closest homolog.…”

Section: Data Collection and Phylogenymentioning

confidence: 99%

Using Evolutionary Information and Ancestral Sequences to Understand the Sequence–Function Relationship in GLP-1 Agonists

Skovgaard

Kodra

Gram

et al. 2006

Journal of Molecular Biology

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Isolation and Structural Characterization of Proglucagon-Derived Peptides, Pancreatic Polypeptide, and Somatostatin from the UrodeleAmphiuma tridactylum

Cited by 29 publications

References 0 publications

The Xenopus proglucagon gene encodes novel GLP-1-like peptides with insulinotropic properties

The Xenopus proglucagon gene encodes novel GLP-1-like peptides with insulinotropic properties

Insights into the evolution of proglucagon‐derived peptides and receptors in fish and amphibians

Using Evolutionary Information and Ancestral Sequences to Understand the Sequence–Function Relationship in GLP-1 Agonists

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