| http://purl.uniprot.org/citations/22509386 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22509386 | http://www.w3.org/2000/01/rdf-schema#comment | "Because of its low relative folding rate and plentiful manufacture in β-cells, proinsulin maintains a homeostatic balance of natively and plentiful non-natively folded states (i.e., proinsulin homeostasis, PIHO) through the integration of maturation and disposal processes. PIHO is susceptible to genetic and environmental influences, and its disorder has been critically linked to defects in β-cells in diabetes. To explore this hypothesis, we performed polymerase chain reaction (PCR), metabolic-labeling, immunoblotting, and histological studies to clarify what defects result from primary disorder of PIHO in model Ins2(+/Akita) β-cells. We used T antigen-transformed Ins2(+/Akita) and control Ins2(+/+) β-cells established from Akita and wild-type littermate mice. In Ins2(+/Akita) β-cells, we found no apparent defect at the transcriptional and translational levels to contribute to reduced cellular content of insulin and its precursor and secreted insulin. Glucose response remained normal in proinsulin biosynthesis but was impaired for insulin secretion. The size and number of mature insulin granules were reduced, but the size/number of endoplasmic reticulum, Golgi, mitochondrion, and lysosome organelles and vacuoles were expanded/increased. Moreover, cell death increased, and severe oxidative stress, which manifested as increased reactive oxygen species, thioredoxin-interacting protein, and protein tyrosine nitration, occurred in Ins2(+/Akita) β-cells and/or islets. These data show the first clear evidence that primary PIHO imbalance induces severe oxidative stress and impairs glucose-stimulated insulin release and β-cell survival as well as producing other toxic consequences. The defects disclosed/clarified in model Ins2(+/Akita) β-cells further support a role of the genetic and stress-susceptible PIHO disorder in β-cell failure and diabetes."xsd:string |
| http://purl.uniprot.org/citations/22509386 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0035098"xsd:string |
| http://purl.uniprot.org/citations/22509386 | http://purl.uniprot.org/core/author | "Liu C."xsd:string |
| http://purl.uniprot.org/citations/22509386 | http://purl.uniprot.org/core/author | "Zhang X."xsd:string |
| http://purl.uniprot.org/citations/22509386 | http://purl.uniprot.org/core/author | "Wang J."xsd:string |
| http://purl.uniprot.org/citations/22509386 | http://purl.uniprot.org/core/author | "Tang W."xsd:string |
| http://purl.uniprot.org/citations/22509386 | http://purl.uniprot.org/core/author | "Yuan Q."xsd:string |
| http://purl.uniprot.org/citations/22509386 | http://purl.uniprot.org/core/author | "Hinson J.A."xsd:string |
| http://purl.uniprot.org/citations/22509386 | http://purl.uniprot.org/core/author | "Osei K."xsd:string |
| http://purl.uniprot.org/citations/22509386 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22509386 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/22509386 | http://purl.uniprot.org/core/pages | "e35098"xsd:string |
| http://purl.uniprot.org/citations/22509386 | http://purl.uniprot.org/core/title | "Proinsulin atypical maturation and disposal induces extensive defects in mouse Ins2+/Akita beta-cells."xsd:string |
| http://purl.uniprot.org/citations/22509386 | http://purl.uniprot.org/core/volume | "7"xsd:string |
| http://purl.uniprot.org/citations/22509386 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22509386 |
| http://purl.uniprot.org/citations/22509386 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/22509386 |
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| http://purl.uniprot.org/uniprot/#_D3Z596-mappedCitation-22509386 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22509386 |
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| http://purl.uniprot.org/uniprot/#_D0EY27-mappedCitation-22509386 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22509386 |
| http://purl.uniprot.org/uniprot/#_Q5EEX1-mappedCitation-22509386 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22509386 |
| http://purl.uniprot.org/uniprot/#_P01326-mappedCitation-22509386 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22509386 |
| http://purl.uniprot.org/uniprot/D0EY27 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/22509386 |