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Stimulation of lipogenesis as well as fatty acid oxidation protects against palmitate-induced INS-1 beta-cell death.
DC Field | Value | Language |
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dc.contributor.author | Choi, SE | - |
dc.contributor.author | Jung, IR | - |
dc.contributor.author | Lee, YJ | - |
dc.contributor.author | Lee, SJ | - |
dc.contributor.author | Lee, JH | - |
dc.contributor.author | Kim, Y | - |
dc.contributor.author | Jun, HS | - |
dc.contributor.author | Lee, KW | - |
dc.contributor.author | Park, CB | - |
dc.contributor.author | Kang, Y | - |
dc.date.accessioned | 2012-04-24T04:24:57Z | - |
dc.date.available | 2012-04-24T04:24:57Z | - |
dc.date.issued | 2011 | - |
dc.identifier.issn | 0013-7227 | - |
dc.identifier.uri | http://repository.ajou.ac.kr/handle/201003/6531 | - |
dc.description.abstract | Saturated fatty acids are generally cytotoxic to β-cells. Accumulation of lipid intermediates and subsequent activation of lipid-mediated signals has been suggested to play a role in fatty acid-induced toxicity. To determine the effects of lipid metabolism in fatty acid-induced toxicity, lipid metabolism was modulated by up- and down-regulation of a lipogenic or fatty acid oxidation pathway, and the effects of various modulators on palmitate (PA)-induced INS-1 β-cell death were then evaluated. Treatment with the liver X receptor agonist T0901317 reduced PA-induced INS-1 cell death, regardless of its enhanced lipogenic activity. Furthermore, transient expression of a lipogenic transcription factor sterol regulatory element binding protein-1c (SREBP-1c) was also protective against PA-induced cytotoxicity. In contrast, knockdown of SREBP-1c or glycerol-3-phosphate acyltransferase 1 significantly augmented PA-induced cell death and reduced T0901317-induced protective effects. Conversely, T0901317 increased carnitine PA transferease-1 (CPT-1) expression and augmented PA oxidation. CPT-1 inhibitor etomoxir or CPT-1 knockdown augmented PA-induced cell death and reduced T0901317-induced protective effects, whereas the peroxisome proliferator-activated receptor (PPAR)-α agonist bezafibrate reduced PA-induced toxicity. In particular, T0901317 reduced the levels of PA-induced endoplasmic reticulum (ER) stress markers, including phospho-eukaryotic initiation factor-2α, phospho-C-Jun N terminal kinase, and CCAAT/enhancer-binding protein homologous protein. In contrast, knockdown of SREBP-1c or glycerol-3-phosphate acyltransferase 1 augmented PA-induced ER stress responses. Results of these experiments suggested that stimulation of lipid metabolism, including lipogenesis and fatty acid oxidation, protected β-cells from PA-induced lipotoxicity and that protection through enhanced lipogenesis was likely due to reduced ER stress. | en |
dc.format | application/pdf | - |
dc.language.iso | en | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Cells, Cultured | - |
dc.subject.MESH | Endoplasmic Reticulum | - |
dc.subject.MESH | Fatty Acids | - |
dc.subject.MESH | Insulin-Secreting Cells | - |
dc.subject.MESH | Lipid Metabolism | - |
dc.subject.MESH | Lipogenesis | - |
dc.subject.MESH | Orphan Nuclear Receptors | - |
dc.subject.MESH | Oxidation-Reduction | - |
dc.subject.MESH | Palmitates | - |
dc.subject.MESH | Rats | - |
dc.title | Stimulation of lipogenesis as well as fatty acid oxidation protects against palmitate-induced INS-1 beta-cell death. | - |
dc.type | Article | - |
dc.identifier.pmid | 21209018 | - |
dc.identifier.url | http://endo.endojournals.org/cgi/pmidlookup?view=long&pmid=21209018 | - |
dc.contributor.affiliatedAuthor | 김, 영수 | - |
dc.contributor.affiliatedAuthor | 이, 관우 | - |
dc.contributor.affiliatedAuthor | 박, 찬배 | - |
dc.contributor.affiliatedAuthor | 강, 엽 | - |
dc.type.local | Journal Papers | - |
dc.identifier.doi | 10.1210/en.2010-0924 | - |
dc.citation.title | Endocrinology | - |
dc.citation.volume | 152 | - |
dc.citation.number | 3 | - |
dc.citation.date | 2011 | - |
dc.citation.startPage | 816 | - |
dc.citation.endPage | 827 | - |
dc.identifier.bibliographicCitation | Endocrinology, 152(3). : 816-827, 2011 | - |
dc.identifier.eissn | 1945-7170 | - |
dc.relation.journalid | J000137227 | - |
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