| http://purl.uniprot.org/citations/28778482 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28778482 | http://www.w3.org/2000/01/rdf-schema#comment | "Elevations in C-reactive protein (CRP) levels are positively correlated with the progress of type 2 diabetes mellitus. However, the effect of CRP on pancreatic insulin secretion is unknown. Here, we showed that purified human CRP impaired insulin secretion in isolated mouse islets and NIT-1 insulin-secreting cells in dose- and time-dependent manners. CRP increased NADPH oxidase-mediated ROS (reactive oxygen species) production, which simultaneously promoted the production of nitrotyrosine (an indicator of RNS, reactive nitrogen species) and TNFα, to diminish cell viability, insulin secretion in islets and insulin-secreting cells. These CRP-mediated detrimental effects on cell viability and insulin secretion were significantly reversed by adding NAC (a potent antioxidant), apocynin (a selective NADPH oxidase inhibitor), L-NAME (a non-selective nitric oxide synthase (NOS) inhibitor), aminoguanidine (a selective iNOS inhibitor), PDTC (a selective NFκB inhibitor) or Enbrel (an anti-TNFα fusion protein). However, CRP-induced ROS production failed to change after adding L-NAME, aminoguanidine or PDTC. In isolated islets and NIT-1 cells, the elevated nitrotyrosine contents by CRP pretreatment were significantly suppressed by adding L-NAME but not PDTC. Conversely, CRP-induced increases in TNF-α production were significantly reversed by administration of PDTC but not L-NAME. In addition, wild-type mice treated with purified human CRP showed significant decreases in the insulin secretion index (HOMA-β cells) and the insulin stimulation index in isolated islets that were reversed by the addition of L-NAME, aminoguanidine or NAC. It is suggested that CRP-activated NADPH-oxidase redox signaling triggers iNOS-mediated RNS and NFκB-mediated proinflammatory cytokine production to cause β cell damage in state of inflammation."xsd:string |
| http://purl.uniprot.org/citations/28778482 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.freeradbiomed.2017.07.032"xsd:string |
| http://purl.uniprot.org/citations/28778482 | http://purl.uniprot.org/core/author | "Chen Y.L."xsd:string |
| http://purl.uniprot.org/citations/28778482 | http://purl.uniprot.org/core/author | "Wang Y.C."xsd:string |
| http://purl.uniprot.org/citations/28778482 | http://purl.uniprot.org/core/author | "Chan P.C."xsd:string |
| http://purl.uniprot.org/citations/28778482 | http://purl.uniprot.org/core/author | "Hsieh P.S."xsd:string |
| http://purl.uniprot.org/citations/28778482 | http://purl.uniprot.org/core/author | "Tian Y.F."xsd:string |
| http://purl.uniprot.org/citations/28778482 | http://purl.uniprot.org/core/author | "Hsu W.N."xsd:string |
| http://purl.uniprot.org/citations/28778482 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28778482 | http://purl.uniprot.org/core/name | "Free Radic Biol Med"xsd:string |
| http://purl.uniprot.org/citations/28778482 | http://purl.uniprot.org/core/pages | "200-211"xsd:string |
| http://purl.uniprot.org/citations/28778482 | http://purl.uniprot.org/core/title | "Importance of NADPH oxidase-mediated redox signaling in the detrimental effect of CRP on pancreatic insulin secretion."xsd:string |
| http://purl.uniprot.org/citations/28778482 | http://purl.uniprot.org/core/volume | "112"xsd:string |
| http://purl.uniprot.org/citations/28778482 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/28778482 |
| http://purl.uniprot.org/citations/28778482 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/28778482 |
| http://purl.uniprot.org/uniprot/#_A0A0R4J1X7-mappedCitation-28778482 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28778482 |
| http://purl.uniprot.org/uniprot/#_Q8CIZ9-mappedCitation-28778482 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28778482 |
| http://purl.uniprot.org/uniprot/A0A0R4J1X7 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/28778482 |
| http://purl.uniprot.org/uniprot/Q8CIZ9 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/28778482 |