| http://purl.uniprot.org/citations/24835010 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24835010 | http://www.w3.org/2000/01/rdf-schema#comment | "Chronic myelogenous leukemia patients treated with tyrosine kinase inhibitor, Imatinib, were shown to have increased serum levels of C-peptide. Imatinib specifically inhibits the tyrosine kinase, c-Abl. However, the mechanism of how Imatinib treatment can lead to increased insulin level is unclear. Specifically, there is little investigation into whether Imatinib directly affects β cells to promote insulin production. In this study, we showed that Imatinib significantly induced insulin expression in both glucose-stimulated and resting β cells. In line with this finding, c-Abl knockdown by siRNA and overexpression of c-Abl markedly enhanced and inhibited insulin expression in β cells, respectively. Unexpectedly, high concentrations of glucose significantly induced c-Abl expression, suggesting c-Abl may play a role in balancing insulin production during glucose stimulation. Further studies demonstrated that c-Abl inhibition did not affect the major insulin gene transcription factor, pancreatic and duodenal homeobox-1 (PDX-1) expression. Of interest, inhibition of c-Abl enhanced NKx2.2 and overexpression of c-Abl in β cells markedly down-regulated NKx2.2, which is a positive regulator for insulin gene expression. Additionally, we found that c-Abl inhibition significantly enhanced the expression of glucose transporter GLUT2 on β cells. Our study demonstrates a previously unrecognized mechanism that controls insulin expression through c-Abl-regulated NKx2.2 and GLUT2. Therapeutic targeting β cell c-Abl could be employed in the treatment of diabetes or β cell tumor, insulinoma."xsd:string |
| http://purl.uniprot.org/citations/24835010 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0097694"xsd:string |
| http://purl.uniprot.org/citations/24835010 | http://purl.uniprot.org/core/author | "Li S."xsd:string |
| http://purl.uniprot.org/citations/24835010 | http://purl.uniprot.org/core/author | "Zhang P."xsd:string |
| http://purl.uniprot.org/citations/24835010 | http://purl.uniprot.org/core/author | "Yuan L."xsd:string |
| http://purl.uniprot.org/citations/24835010 | http://purl.uniprot.org/core/author | "Xie C."xsd:string |
| http://purl.uniprot.org/citations/24835010 | http://purl.uniprot.org/core/author | "Xia T."xsd:string |
| http://purl.uniprot.org/citations/24835010 | http://purl.uniprot.org/core/author | "Xia C.Q."xsd:string |
| http://purl.uniprot.org/citations/24835010 | http://purl.uniprot.org/core/author | "Clare-Salzler M.J."xsd:string |
| http://purl.uniprot.org/citations/24835010 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24835010 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/24835010 | http://purl.uniprot.org/core/pages | "e97694"xsd:string |
| http://purl.uniprot.org/citations/24835010 | http://purl.uniprot.org/core/title | "C-Abl inhibitor imatinib enhances insulin production by beta cells: c-Abl negatively regulates insulin production via interfering with the expression of NKx2.2 and GLUT-2."xsd:string |
| http://purl.uniprot.org/citations/24835010 | http://purl.uniprot.org/core/volume | "9"xsd:string |
| http://purl.uniprot.org/citations/24835010 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24835010 |
| http://purl.uniprot.org/citations/24835010 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/24835010 |
| http://purl.uniprot.org/uniprot/#_P42586-mappedCitation-24835010 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24835010 |
| http://purl.uniprot.org/uniprot/#_P00520-mappedCitation-24835010 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24835010 |
| http://purl.uniprot.org/uniprot/#_P14246-mappedCitation-24835010 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24835010 |
| http://purl.uniprot.org/uniprot/#_Q3TM13-mappedCitation-24835010 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24835010 |
| http://purl.uniprot.org/uniprot/#_Q3TRC3-mappedCitation-24835010 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24835010 |
| http://purl.uniprot.org/uniprot/#_Q8K3N8-mappedCitation-24835010 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24835010 |
| http://purl.uniprot.org/uniprot/#_Q3SYK5-mappedCitation-24835010 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24835010 |
| http://purl.uniprot.org/uniprot/#_Q9JKR0-mappedCitation-24835010 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24835010 |