http://purl.uniprot.org/citations/21839170 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/21839170 | http://www.w3.org/2000/01/rdf-schema#comment | "NADH-cytochrome b5 oxidoreductase (Ncb5or) is an endoplasmic reticulum (ER)-associated redox enzyme involved in fatty acid metabolism, and phenotypic abnormalities of Ncb5or(-/-) mice include diabetes and lipoatrophy. These mice are lean and insulin-sensitive but become hyperglycemic at age 7 weeks as a result of β-cell dysfunction and loss. Here we examine early cellular and molecular events associated with manifestations of β-cell defects in Ncb5or(-/-) mice. We observe lower islet β-cell content in pancreata at age 4 weeks and prominent ER distention in β-cells by age 5 weeks. Ultrastructural changes progress rapidly in severity from age 5 to 6 weeks, and their frequency rises from 10% of β-cells at 5 weeks to 33% at 6 weeks. These changes correlate temporally with the onset of diabetes. ER stress responses and lipid load in Ncb5or(-/-) β-cells were assessed with isolated islets from mice at age 5 weeks. Expression levels of the stress marker protein Grp78/BiP and of phosphorylated eIF2α protein were found to be reduced, although their transcript levels did not decline. This pattern stands in contrast to the canonical unfolded protein response. Ncb5or(-/-) β-cells also accumulated higher intracellular levels of palmitate and other free fatty acids and exhibited greater reactive oxygen species production than wild-type cells. An alloxan-susceptible genetic background was found to confer accelerated onset of diabetes in Ncb5or(-/-) mice. These findings provide the first direct evidence that manifestations of diabetes in lean Ncb5or(-/-) mice involve saturated free fatty acid overload of β-cells and ER and oxidative stress responses."xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.bbadis.2011.07.016"xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/author | "Guo Y."xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/author | "Huang H.H."xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/author | "Xu M."xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/author | "Zhu H."xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/author | "Wang W."xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/author | "Turk J."xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/author | "Ding H."xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/author | "Bunn H.F."xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/author | "Mathews C.E."xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/author | "Jiang Z.G."xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/author | "Larade K."xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/author | "Novikova L."xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/author | "Stehno-Bittel L."xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/author | "Thayer T.C."xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/author | "Aires D."xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/author | "Frontera J.R."xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/name | "Biochim Biophys Acta"xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/pages | "1532-1541"xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/title | "Development of diabetes in lean Ncb5or-null mice is associated with manifestations of endoplasmic reticulum and oxidative stress in beta cells."xsd:string |
http://purl.uniprot.org/citations/21839170 | http://purl.uniprot.org/core/volume | "1812"xsd:string |
http://purl.uniprot.org/citations/21839170 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21839170 |