Changes in the ghrelin hormone pathway maybe part of an unusual gastric system in monotremes
- He, Chuan, Tsend-Ayush, Enkhjargal, Myers, Mark, Forbes, Briony, Grützner, Frank
- Authors: He, Chuan , Tsend-Ayush, Enkhjargal , Myers, Mark , Forbes, Briony , Grützner, Frank
- Date: 2013
- Type: Text , Journal article
- Relation: General and Comparative Endocrinology Vol. 191, no. (2013), p. 74-82
- Full Text:
- Reviewed:
- Description: Ghrelin is a growth hormone (GH)-releasing and appetite-regulating peptide predominately released from the stomach. Ghrelin is evolutionarily highly conserved and known to have a wide range of functions including the regulation of metabolism by maintaining an insulin-glucose balance. The peptide is produced as a single proprotein, which is later proteolytically cleaved. Ghrelin exerts its biological function after O-n-octanoylation at residue serine 3, which is catalyzed by ghrelin O-acyl transferase (GOAT) and allows binding to the growth hormone secretagogue receptor (GHS-R 1a). Genes involved in the ghrelin pathway have been identified in a broad range of vertebrate species, however, little is known about this pathway in the basal mammalian lineage of monotremes (platypus and echidna). Monotremes are particularly interesting in this context, as they have undergone massive changes in stomach anatomy and physiology, accompanied by a striking loss of genes involved in gastric function. In this study, we investigated genes in the ghrelin pathway in monotremes. Using degenerate PCR, database searches and synteny analysis we found that genes encoding ghrelin and GOAT are missing in the platypus genome, whilst, as has been reported in other species, the GHSR is present and expressed in brain, pancreas, kidney, intestine, heart and stomach. This is the first report suggesting the loss of ghrelin in a mammal. The loss of this gene may be related to changes to the platypus digestive system and raises questions about the control of blood glucose levels and insulin response in monotreme mammals. In addition, the conservation of the ghrelin receptor gene in platypus indicates that another ligand(s) maybe acting via this receptor in monotremes. © 2013 Elsevier Inc.
- Description: 2003011207
- Authors: He, Chuan , Tsend-Ayush, Enkhjargal , Myers, Mark , Forbes, Briony , Grützner, Frank
- Date: 2013
- Type: Text , Journal article
- Relation: General and Comparative Endocrinology Vol. 191, no. (2013), p. 74-82
- Full Text:
- Reviewed:
- Description: Ghrelin is a growth hormone (GH)-releasing and appetite-regulating peptide predominately released from the stomach. Ghrelin is evolutionarily highly conserved and known to have a wide range of functions including the regulation of metabolism by maintaining an insulin-glucose balance. The peptide is produced as a single proprotein, which is later proteolytically cleaved. Ghrelin exerts its biological function after O-n-octanoylation at residue serine 3, which is catalyzed by ghrelin O-acyl transferase (GOAT) and allows binding to the growth hormone secretagogue receptor (GHS-R 1a). Genes involved in the ghrelin pathway have been identified in a broad range of vertebrate species, however, little is known about this pathway in the basal mammalian lineage of monotremes (platypus and echidna). Monotremes are particularly interesting in this context, as they have undergone massive changes in stomach anatomy and physiology, accompanied by a striking loss of genes involved in gastric function. In this study, we investigated genes in the ghrelin pathway in monotremes. Using degenerate PCR, database searches and synteny analysis we found that genes encoding ghrelin and GOAT are missing in the platypus genome, whilst, as has been reported in other species, the GHSR is present and expressed in brain, pancreas, kidney, intestine, heart and stomach. This is the first report suggesting the loss of ghrelin in a mammal. The loss of this gene may be related to changes to the platypus digestive system and raises questions about the control of blood glucose levels and insulin response in monotreme mammals. In addition, the conservation of the ghrelin receptor gene in platypus indicates that another ligand(s) maybe acting via this receptor in monotremes. © 2013 Elsevier Inc.
- Description: 2003011207
Monotreme glucagon-like peptide-1 in venom and gut : One gene - Two very different functions
- Tsend-Ayush, Enkhjargal, He, Chuan, Myers, Mark, Andrikopoulos, Sof, Wong, Nicole, Sexton, Patrick, Wootten, Denise, Forbes, Briony, Grutzner, Frank
- Authors: Tsend-Ayush, Enkhjargal , He, Chuan , Myers, Mark , Andrikopoulos, Sof , Wong, Nicole , Sexton, Patrick , Wootten, Denise , Forbes, Briony , Grutzner, Frank
- Date: 2016
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 6, no. (2016), p. 1-12
- Full Text:
- Reviewed:
- Description: 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. © The Author(s) 2016.
- Authors: Tsend-Ayush, Enkhjargal , He, Chuan , Myers, Mark , Andrikopoulos, Sof , Wong, Nicole , Sexton, Patrick , Wootten, Denise , Forbes, Briony , Grutzner, Frank
- Date: 2016
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 6, no. (2016), p. 1-12
- Full Text:
- Reviewed:
- Description: 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. © The Author(s) 2016.
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