| http://purl.uniprot.org/citations/26446275 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26446275 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26446275 | http://www.w3.org/2000/01/rdf-schema#comment | "Glucagon antagonism is a potential treatment for diabetes. One potential side effect is α-cell hyperplasia, which has been noted in several approaches to antagonize glucagon action. To investigate the molecular mechanism of the α-cell hyperplasia and to identify the responsible factor, we created a zebrafish model in which glucagon receptor (gcgr) signaling has been interrupted. The genetically and chemically tractable zebrafish, which provides a robust discovery platform, has two gcgr genes (gcgra and gcgrb) in its genome. Sequence, phylogenetic, and synteny analyses suggest that these are co-orthologs of the human GCGR. Similar to its mammalian counterparts, gcgra and gcgrb are mainly expressed in the liver. We inactivated the zebrafish gcgra and gcgrb using transcription activator-like effector nuclease (TALEN) first individually and then both genes, and assessed the number of α-cells using an α-cell reporter line, Tg(gcga:GFP). Compared to WT fish at 7 days postfertilization, there were more α-cells in gcgra-/-, gcgrb-/-, and gcgra-/-;gcgrb-/-fish and there was an increased rate of α-cell proliferation in the gcgra-/-;gcgrb-/-fish. Glucagon levels were higher but free glucose levels were lower in gcgra-/-, gcgrb-/-, and gcgra-/-;gcgrb-/- fish, similar to Gcgr-/-mice. These results indicate that the compensatory α-cell hyperplasia in response to interruption of glucagon signaling is conserved in zebrafish. The robust α-cell hyperplasia in gcgra-/-;gcgrb-/-larvae provides a platform to screen for chemical and genetic suppressors, and ultimately to identify the stimulus of α-cell hyperplasia and its signaling mechanism."xsd:string |
| http://purl.uniprot.org/citations/26446275 | http://purl.org/dc/terms/identifier | "doi:10.1530/joe-15-0284"xsd:string |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/author | "Chen W."xsd:string |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/author | "Chen W."xsd:string |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/author | "Li M."xsd:string |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/author | "Li M."xsd:string |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/author | "Zhao L."xsd:string |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/author | "Zhao L."xsd:string |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/author | "Powers A.C."xsd:string |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/author | "Powers A.C."xsd:string |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/author | "Nicholson W.E."xsd:string |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/author | "Nicholson W.E."xsd:string |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/author | "Dean E.D."xsd:string |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/author | "Dean E.D."xsd:string |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/name | "J. Endocrinol."xsd:string |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/name | "J Endocrinol"xsd:string |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/pages | "93-103"xsd:string |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/pages | "93-103"xsd:string |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/title | "Glucagon receptor inactivation leads to alpha-cell hyperplasia in zebrafish."xsd:string |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/title | "Glucagon receptor inactivation leads to alpha-cell hyperplasia in zebrafish."xsd:string |
| http://purl.uniprot.org/citations/26446275 | http://purl.uniprot.org/core/volume | "227"xsd:string |