Journal article
Monotreme glucagon-like peptide-1 in venom and gut: One gene - Two very different functions
E Tsend-Ayush, C He, MA Myers, S Andrikopoulos, N Wong, PM Sexton, D Wootten, BE Forbes, F Grutzner
Scientific Reports | NATURE PORTFOLIO | Published : 2016
DOI: 10.1038/srep37744
Abstract
The importance of Glucagon like peptide 1 (GLP-1) for metabolic control and insulin release sparked the evolution of genes mimicking GLP-1 action in venomous species (e.g. Exendin-4 in Heloderma suspectum (gila monster)). We discovered that platypus and echidna express a single GLP-1 peptide in both intestine and venom. Specific changes in GLP-1 of monotreme mammals result in resistance to DPP-4 cleavage which is also observed in the GLP-1 like Exendin-4 expressed in Heloderma venom. Remarkably we discovered that monotremes evolved an alternative mechanism to degrade GLP-1. We also show that monotreme GLP-1 stimulates insulin release in cultured rodent islets, but surprisingly shows low rece..
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Funding Acknowledgements
We acknowledge the contribution of Assoc. Prof. Catherine Abbott and Dr Melissa Pitman (Flinders University of South Australia) for their gift of recombinant human DPP-4 and advice on DPP-4, Prof Dominic Geraghty (University of Tasmania) and Dr Nick Gust (Department of Primary Industries, Parks Water and Environment) for platypus serum, Ms Carlie Sawtell for echidna Gcg PCR analysis, Dr Tasman Daish and Dr Aaron Casey for tissue collection, and the China Scholarships Council and Adelaide University for supporting Chuan He.