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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

Authors
Lee, MS; Choi, SE; Ha, ES; An, SY; Kim, TH; Han, SJ; Kim, HJ; Kim, DJ; Kang, Y; Lee, KW
Citation
Metabolism: clinical and experimental, 61(8):1142-1151, 2012
Journal Title
Metabolism: clinical and experimental
ISSN
0026-04951532-8600
Abstract
We 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.
MeSH terms
4-Chloro-7-nitrobenzofurazan/analogs & derivatives/metabolismBlotting, WesternDeoxyglucose/analogs & derivatives/metabolismEnzyme ActivationGlucose Transporter Type 1/metabolismGlucose Transporter Type 4/metabolismHumansI-kappa B Kinase/metabolismInsulin/*metabolism*Insulin ResistanceMAP Kinase Kinase 4/metabolismMuscle Fibers, Skeletal/*metabolismNF-kappa B p50 Subunit/*antagonists & inhibitorsPalmitic AcidPhosphorylationPolymerase Chain Reaction/methodsProto-Oncogene Proteins c-akt/*antagonists & inhibitorsRNA, Small Interfering/metabolism
DOI
10.1016/j.metabol.2012.01.012
PMID
22398021
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Endocrinology & Metabolism
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
이, 민석안, 소연한, 승진김, 혜진김, 대중강, 엽이, 관우
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