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Supplement of TCA cycle intermediates protects against high glucose/palmitate-induced INS-1 beta cell death.

DC Field Value Language
dc.contributor.authorChoi, SE-
dc.contributor.authorLee, YJ-
dc.contributor.authorHwang, GS-
dc.contributor.authorChung, JH-
dc.contributor.authorLee, SJ-
dc.contributor.authorLee, JH-
dc.contributor.authorHan, SJ-
dc.contributor.authorKim, HJ-
dc.contributor.authorLee, KW-
dc.contributor.authorKim, Y-
dc.contributor.authorJun, HS-
dc.contributor.authorKang, Y-
dc.date.accessioned2012-04-24T02:24:16Z-
dc.date.available2012-04-24T02:24:16Z-
dc.date.issued2011-
dc.identifier.issn0003-9861-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/6527-
dc.description.abstractThe aim of this study is to investigate the effect of mitochondrial metabolism on high glucose/palmitate (HG/PA)-induced INS-1 beta cell death. Long-term treatment of INS-1 cells with HG/PA impaired energy-producing metabolism accompanying with depletion of TCA cycle intermediates. Whereas an inhibitor of carnitine palmitoyl transferase 1 augmented HG/PA-induced INS-1 cell death, stimulators of fatty acid oxidation protected the cells against the HG/PA-induced death. Furthermore, whereas mitochondrial pyruvate carboxylase inhibitor phenylacetic acid augmented HG/PA-induced INS-1 cell death, supplementation of TCA cycle metabolites including leucine/glutamine, methyl succinate/α-ketoisocaproic acid, dimethyl malate, and valeric acid or treatment with a glutamate dehydrogenase activator, aminobicyclo-heptane-2-carboxylic acid (BCH), significantly protected the cells against the HG/PA-induced death. In particular, the mitochondrial tricarboxylate carrier inhibitor, benzene tricarboxylate (BTA), also showed a strong protective effect on the HG/PA-induced INS-1 cell death. Knockdown of glutamate dehydrogenase or tricarboxylate carrier augmented or reduced the HG/PA-induced INS-1 cell death, respectively. Both BCH and BTA restored HG/PA-induced reduction of energy metabolism as well as depletion of TCA intermediates. These data suggest that depletion of the TCA cycle intermediate pool and impaired energy-producing metabolism may play a role in HG/PA-induced cytotoxicity to beta cells and thus, HG/PA-induced beta cell glucolipotoxicity can be protected by nutritional or pharmacological maneuver enhancing anaplerosis or reducing cataplerosis.-
dc.language.isoen-
dc.subject.MESHAdenosine Triphosphate/metabolism-
dc.subject.MESHAnimals-
dc.subject.MESHBenzene Derivatives/pharmacology-
dc.subject.MESHCarboxylic Acids/pharmacology-
dc.subject.MESHCarrier Proteins/genetics-
dc.subject.MESHCell Death/*drug effects-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESH*Citric Acid Cycle/drug effects-
dc.subject.MESHDose-Response Relationship, Drug-
dc.subject.MESHDrug Interactions-
dc.subject.MESHEnergy Metabolism/drug effects-
dc.subject.MESHGene Knockdown Techniques-
dc.subject.MESHGlucose/metabolism/*toxicity-
dc.subject.MESHGlutamate Dehydrogenase/deficiency/genetics-
dc.subject.MESHInsulin-Secreting Cells/*cytology/*drug effects/metabolism-
dc.subject.MESHMitochondria/drug effects/metabolism-
dc.subject.MESHOxidation-Reduction/drug effects-
dc.subject.MESHPalmitates/metabolism/*toxicity-
dc.subject.MESHRats-
dc.subject.MESHTricarboxylic Acids/pharmacology-
dc.titleSupplement of TCA cycle intermediates protects against high glucose/palmitate-induced INS-1 beta cell death.-
dc.typeArticle-
dc.identifier.pmid20965146-
dc.identifier.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0003-9861(10)00439-X-
dc.contributor.affiliatedAuthor한, 승진-
dc.contributor.affiliatedAuthor김, 혜진-
dc.contributor.affiliatedAuthor이, 관우-
dc.contributor.affiliatedAuthor강, 엽-
dc.type.localJournal Papers-
dc.identifier.doi10.1016/j.abb.2010.10.011-
dc.citation.titleArchives of biochemistry and biophysics-
dc.citation.volume505-
dc.citation.number2-
dc.citation.date2011-
dc.citation.startPage231-
dc.citation.endPage241-
dc.identifier.bibliographicCitationArchives of biochemistry and biophysics, 505(2):231-241, 2011-
dc.identifier.eissn1096-0384-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Endocrinology & Metabolism
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
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