| http://purl.uniprot.org/citations/21700708 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21700708 | http://www.w3.org/2000/01/rdf-schema#comment | "Insulin receptor substrate-2 (IRS-2) plays a critical role in the survival and function of pancreatic β-cells. Gene disruption of IRS-2 results in failure of the β-cell compensatory mechanism and diabetes. Nonetheless, the regulation of IRS-2 protein expression in β-cells remains largely unknown. Inducible nitric-oxide synthase (iNOS), a major mediator of inflammation, has been implicated in β-cell damage in type 1 and type 2 diabetes. The effects of iNOS on IRS-2 expression have not yet been investigated in β-cells. Here, we show that iNOS and NO donor decreased IRS-2 protein expression in INS-1/832 insulinoma cells and mouse islets, whereas IRS-2 mRNA levels were not altered. Interleukin-1β (IL-1β), alone or in combination with interferon-γ (IFN-γ), reduced IRS-2 protein expression in an iNOS-dependent manner without altering IRS-2 mRNA levels. Proteasome inhibitors, MG132 and lactacystin, blocked the NO donor-induced reduction in IRS-2 protein expression. Treatment with NO donor led to activation of glycogen synthase kinase-3β (GSK-3β) and c-Jun N-terminal kinase (JNK/SAPK) in β-cells. Inhibition of GSK-3β by pharmacological inhibitors or siRNA-mediated knockdown significantly prevented NO donor-induced reduction in IRS-2 expression in β-cells. In contrast, a JNK inhibitor, SP600125, did not effectively block reduced IRS-2 expression in NO donor-treated β-cells. These data indicate that iNOS-derived NO reduces IRS-2 expression by promoting protein degradation, at least in part, through a GSK-3β-dependent mechanism. Our findings suggest that iNOS-mediated decreased IRS-2 expression may contribute to the progression and/or exacerbation of β-cell failure in diabetes."xsd:string |
| http://purl.uniprot.org/citations/21700708 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m110.192732"xsd:string |
| http://purl.uniprot.org/citations/21700708 | http://purl.uniprot.org/core/author | "Kim M."xsd:string |
| http://purl.uniprot.org/citations/21700708 | http://purl.uniprot.org/core/author | "Shimizu N."xsd:string |
| http://purl.uniprot.org/citations/21700708 | http://purl.uniprot.org/core/author | "Tamura Y."xsd:string |
| http://purl.uniprot.org/citations/21700708 | http://purl.uniprot.org/core/author | "Fukaya M."xsd:string |
| http://purl.uniprot.org/citations/21700708 | http://purl.uniprot.org/core/author | "Kitamura T."xsd:string |
| http://purl.uniprot.org/citations/21700708 | http://purl.uniprot.org/core/author | "Mao J."xsd:string |
| http://purl.uniprot.org/citations/21700708 | http://purl.uniprot.org/core/author | "Shinozaki S."xsd:string |
| http://purl.uniprot.org/citations/21700708 | http://purl.uniprot.org/core/author | "Tanioka T."xsd:string |
| http://purl.uniprot.org/citations/21700708 | http://purl.uniprot.org/core/author | "Kaneki M."xsd:string |
| http://purl.uniprot.org/citations/21700708 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21700708 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/21700708 | http://purl.uniprot.org/core/pages | "29388-29396"xsd:string |
| http://purl.uniprot.org/citations/21700708 | http://purl.uniprot.org/core/title | "Inducible nitric-oxide synthase and nitric oxide donor decrease insulin receptor substrate-2 protein expression by promoting proteasome-dependent degradation in pancreatic beta-cells: involvement of glycogen synthase kinase-3beta."xsd:string |
| http://purl.uniprot.org/citations/21700708 | http://purl.uniprot.org/core/volume | "286"xsd:string |
| http://purl.uniprot.org/citations/21700708 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21700708 |
| http://purl.uniprot.org/citations/21700708 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/21700708 |
| http://purl.uniprot.org/uniprot/#_D0FZQ3-mappedCitation-21700708 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21700708 |
| http://purl.uniprot.org/uniprot/#_A0A1L1STZ4-mappedCitation-21700708 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21700708 |
| http://purl.uniprot.org/uniprot/#_D3YC69-mappedCitation-21700708 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21700708 |
| http://purl.uniprot.org/uniprot/#_A0A338P6P8-mappedCitation-21700708 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21700708 |
| http://purl.uniprot.org/uniprot/#_A0A3B3ITW1-mappedCitation-21700708 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21700708 |
| http://purl.uniprot.org/uniprot/#_A2AV66-mappedCitation-21700708 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21700708 |