| http://purl.uniprot.org/citations/26900721 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26900721 | http://www.w3.org/2000/01/rdf-schema#comment | "The islet in type 2 diabetes is characterized by β-cell loss, increased β-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). When protein misfolding protective mechanisms are overcome, human IAPP (h-IAPP) forms membrane permeant toxic oligomers that induce β-cell dysfunction and apoptosis. In humans with type 2 diabetes (T2D) and mice transgenic for h-IAPP, endoplasmic reticulum (ER) stress has been inferred from nuclear translocation of CCAAT/enhancer-binding protein homologous protein (CHOP), an established mediator of ER stress. To establish whether h-IAPP toxicity is mediated by ER stress, we evaluated diabetes onset and β-cell mass in h-IAPP transgenic (h-TG) mice with and without deletion of CHOP in comparison with wild-type controls. Diabetes was delayed in h-TG CHOP(-/-) mice, with relatively preserved β-cell mass and decreased β-cell apoptosis. Deletion of CHOP attenuates dysfunction of the autophagy/lysosomal pathway in β-cells of h-TG mice, uncovering a role for CHOP in mediating h-IAPP-induced dysfunction of autophagy. As deletion of CHOP delayed but did not prevent h-IAPP-induced β-cell loss and diabetes, we examined CHOP-independent stress pathways. JNK, a target of the IRE-1pTRAF2 complex, and the Bcl-2 family proapoptotic mediator BIM, a target of ATF4, were comparably activated by h-IAPP expression in the presence and absence of CHOP. Therefore, although these studies affirm that CHOP is a mediator of h-IAPP-induced ER stress, it is not the only one. Therefore, suppression of CHOP alone is unlikely to be a durable therapeutic strategy to protect against h-IAPP toxicity because multiple stress pathways are activated."xsd:string |
| http://purl.uniprot.org/citations/26900721 | http://purl.org/dc/terms/identifier | "doi:10.1210/me.2015-1255"xsd:string |
| http://purl.uniprot.org/citations/26900721 | http://purl.uniprot.org/core/author | "Cory M."xsd:string |
| http://purl.uniprot.org/citations/26900721 | http://purl.uniprot.org/core/author | "Rivera J.F."xsd:string |
| http://purl.uniprot.org/citations/26900721 | http://purl.uniprot.org/core/author | "Costes S."xsd:string |
| http://purl.uniprot.org/citations/26900721 | http://purl.uniprot.org/core/author | "Butler P.C."xsd:string |
| http://purl.uniprot.org/citations/26900721 | http://purl.uniprot.org/core/author | "Hoang J."xsd:string |
| http://purl.uniprot.org/citations/26900721 | http://purl.uniprot.org/core/author | "Butler A.E."xsd:string |
| http://purl.uniprot.org/citations/26900721 | http://purl.uniprot.org/core/author | "Gurlo T."xsd:string |
| http://purl.uniprot.org/citations/26900721 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/26900721 | http://purl.uniprot.org/core/name | "Mol Endocrinol"xsd:string |
| http://purl.uniprot.org/citations/26900721 | http://purl.uniprot.org/core/pages | "446-454"xsd:string |
| http://purl.uniprot.org/citations/26900721 | http://purl.uniprot.org/core/title | "CHOP Contributes to, But Is Not the Only Mediator of, IAPP Induced beta-Cell Apoptosis."xsd:string |
| http://purl.uniprot.org/citations/26900721 | http://purl.uniprot.org/core/volume | "30"xsd:string |
| http://purl.uniprot.org/citations/26900721 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26900721 |
| http://purl.uniprot.org/citations/26900721 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/26900721 |
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