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Fibroblast growth factor-21 protects human skeletal muscle myotubes from palmitate-induced insulin resistance by inhibiting stress kinase and NF-κB

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dc.contributor.authorLee, MS-
dc.contributor.authorChoi, SE-
dc.contributor.authorHa, ES-
dc.contributor.authorAn, SY-
dc.contributor.authorKim, TH-
dc.contributor.authorHan, SJ-
dc.contributor.authorKim, HJ-
dc.contributor.authorKim, DJ-
dc.contributor.authorKang, Y-
dc.contributor.authorLee, KW-
dc.date.accessioned2013-04-22T23:53:00Z-
dc.date.available2013-04-22T23:53:00Z-
dc.date.issued2012-
dc.identifier.issn0026-0495-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/7819-
dc.description.abstractWe investigated the effects of fibroblast growth factor-21 (FGF-21) on palmitate-induced insulin resistance in skeletal muscle myotubes. First, to determine the effect of FGF-21 on palmitate-induced insulin resistance, we measured 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose uptake and levels of proteins involved in insulin signaling pathways (IRS-1 and Akt) in human skeletal muscle myotubes (HSMMs) exposed to palmitate for 24h, and compared HSMMs exposed to palmitate and different doses of recombinant FGF-21. Second, to determine the mechanisms underlying the contribution of FGF-21 to palmitate-induced insulin resistance, we compared levels of proteins linked to palmitate-induced insulin resistance (PKC-θ, IKKα/β, JNK, p38, IκBα, and NF-κB) in HSMMs exposed to palmitate and different doses of recombinant FGF-21 for 24h. Palmitate-reduced glucose uptake was restored by FGF-21. Palmitate inhibited phosphorylation of Akt and thereby impaired insulin signaling in HSMMs. FGF-21 prevented palmitate from inhibiting the phosphorylation of Akt. These results indicate that FGF-21 prevented palmitate-induced insulin resistance in HSMMs. Palmitate activated NF-κB in HSMMs, thereby impairing the action of insulin and initiating chronic inflammation. FGF-21 inhibited palmitate-induced NF-κB activation in HSMMs. The results of the present study suggest that FGF-21 prevents palmitate-induced insulin resistance in HSMMs by inhibiting the activation of stress kinase and NF-κB.-
dc.language.isoen-
dc.subject.MESH4-Chloro-7-nitrobenzofurazan-
dc.subject.MESHBlotting, Western-
dc.subject.MESHDeoxyglucose-
dc.subject.MESHEnzyme Activation-
dc.subject.MESHGlucose Transporter Type 1-
dc.subject.MESHGlucose Transporter Type 4-
dc.subject.MESHHumans-
dc.subject.MESHI-kappa B Kinase-
dc.subject.MESHInsulin-
dc.subject.MESHInsulin Resistance-
dc.subject.MESHMAP Kinase Kinase 4-
dc.subject.MESHMuscle Fibers, Skeletal-
dc.subject.MESHNF-kappa B p50 Subunit-
dc.subject.MESHPalmitic Acid-
dc.subject.MESHPhosphorylation-
dc.subject.MESHPolymerase Chain Reaction-
dc.subject.MESHProto-Oncogene Proteins c-akt-
dc.subject.MESHRNA, Small Interfering-
dc.titleFibroblast growth factor-21 protects human skeletal muscle myotubes from palmitate-induced insulin resistance by inhibiting stress kinase and NF-κB-
dc.typeArticle-
dc.identifier.pmid22398021-
dc.identifier.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0026-0495(12)00040-6-
dc.contributor.affiliatedAuthor이, 민석-
dc.contributor.affiliatedAuthor안, 소연-
dc.contributor.affiliatedAuthor한, 승진-
dc.contributor.affiliatedAuthor김, 혜진-
dc.contributor.affiliatedAuthor김, 대중-
dc.contributor.affiliatedAuthor강, 엽-
dc.contributor.affiliatedAuthor이, 관우-
dc.type.localJournal Papers-
dc.identifier.doi10.1016/j.metabol.2012.01.012-
dc.citation.titleMetabolism: clinical and experimental-
dc.citation.volume61-
dc.citation.number8-
dc.citation.date2012-
dc.citation.startPage1142-
dc.citation.endPage1151-
dc.identifier.bibliographicCitationMetabolism: clinical and experimental, 61(8). : 1142-1151, 2012-
dc.identifier.eissn1532-8600-
dc.relation.journalidJ000260495-
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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