| http://purl.uniprot.org/citations/22547676 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22547676 | http://www.w3.org/2000/01/rdf-schema#comment | "The biallelic expression of the imprinted gene ZAC1/PLAGL1 underlies ≈ 60% of all cases of transient neonatal diabetes mellitus (TNDM) that present with low perinatal insulin secretion. Molecular targets of ZAC1 misexpression in pancreatic β cells are unknown. Here, we identified the guanine nucleotide exchange factor Rasgrf1 as a direct Zac1/Plagl1 target gene in murine β cells. Doubling Zac1 expression reduced Rasgrf1 expression, the stimulus-induced activation of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways, and, ultimately, insulin secretion. Normalizing Rasgrf1 expression reversed this phenotype. Moreover, the transplantation of Zac1-overexpressing β cells failed to reinstate euglycemia in experimental diabetic mice. In contrast, Zac1 expression did not interfere with the signaling of the glucagon-like peptide 1 receptor (GLP-1R), and the GLP-1 analog liraglutide improved hyperglycemia in transplanted experimental diabetic mice. This study unravels a mechanism contributing to insufficient perinatal insulin secretion in TNDM and raises new prospects for therapy."xsd:string |
| http://purl.uniprot.org/citations/22547676 | http://purl.org/dc/terms/identifier | "doi:10.1128/mcb.06637-11"xsd:string |
| http://purl.uniprot.org/citations/22547676 | http://purl.uniprot.org/core/author | "Hoffmann A."xsd:string |
| http://purl.uniprot.org/citations/22547676 | http://purl.uniprot.org/core/author | "Spengler D."xsd:string |
| http://purl.uniprot.org/citations/22547676 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22547676 | http://purl.uniprot.org/core/name | "Mol Cell Biol"xsd:string |
| http://purl.uniprot.org/citations/22547676 | http://purl.uniprot.org/core/pages | "2549-2560"xsd:string |
| http://purl.uniprot.org/citations/22547676 | http://purl.uniprot.org/core/title | "Transient neonatal diabetes mellitus gene Zac1 impairs insulin secretion in mice through Rasgrf1."xsd:string |
| http://purl.uniprot.org/citations/22547676 | http://purl.uniprot.org/core/volume | "32"xsd:string |
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