Monotreme glucagon-like peptide-1 in venom and gut: one gene – two very different functions
| Autor: | Mark A. Myers, Patrick M. Sexton, Chuan He, Frank Grützner, Enkhjargal Tsend-Ayush, Sof Andrikopoulos, Briony E. Forbes, Denise Wootten, Nicole Wong |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
endocrine system Tachyglossidae 030209 endocrinology & metabolism Venom Peptide Monotreme Incretins Article 03 medical and health sciences 0302 clinical medicine Glucagon-Like Peptide 1 biology.animal Gene duplication Insulin Secretion Gila monster Animals Insulin Intestinal Mucosa Selection Genetic Platypus Gene Cells Cultured Phylogeny chemistry.chemical_classification Multidisciplinary biology Monotremata Venoms digestive oral and skin physiology Anatomy biology.organism_classification Biological Evolution Cell biology 030104 developmental biology chemistry Echidna Exenatide Peptides hormones hormone substitutes and hormone antagonists |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep37744 |
| Popis: | 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 receptor affinity and bias toward Erk signaling. We propose that these changes in monotreme GLP-1 are the result of conflicting function of this peptide in metabolic control and venom. This evolutionary path is fundamentally different from the generally accepted idea that conflicting functions in a single gene favour duplication and diversification, as is the case for Exendin-4 in gila monster. This provides novel insight into the remarkably different metabolic control mechanism and venom function in monotremes and an unique example of how different selective pressures act upon a single gene in the absence of gene duplication. |
| Databáze: | OpenAIRE |
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