| pubmed-article:20805226 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20805226 | lifeskim:mentions | umls-concept:C1704336 | lld:lifeskim |
| pubmed-article:20805226 | lifeskim:mentions | umls-concept:C0013081 | lld:lifeskim |
| pubmed-article:20805226 | lifeskim:mentions | umls-concept:C0221099 | lld:lifeskim |
| pubmed-article:20805226 | lifeskim:mentions | umls-concept:C1420175 | lld:lifeskim |
| pubmed-article:20805226 | lifeskim:mentions | umls-concept:C0536670 | lld:lifeskim |
| pubmed-article:20805226 | lifeskim:mentions | umls-concept:C0599896 | lld:lifeskim |
| pubmed-article:20805226 | pubmed:issue | 45 | lld:pubmed |
| pubmed-article:20805226 | pubmed:dateCreated | 2010-11-1 | lld:pubmed |
| pubmed-article:20805226 | pubmed:abstractText | Elevated saturated FFAs including palmitate (C16:0) are a primary trigger for peripheral insulin resistance characterized by impaired glucose uptake/disposal in skeletal muscle, resulting from impaired GLUT4 translocation in response to insulin. We herein demonstrate that palmitate induces down-regulation of sortilin, a sorting receptor implicated in the formation of insulin-responsive GLUT4 vesicles, via mechanisms involving PKC and TNF-?-converting enzyme, but not p38, JNK, or mitochondrial reactive oxygen species generation, leading to impaired GLUT4 trafficking in C2C12 myotubes. Intriguingly, unsaturated FFAs such as palmitoleate (C16:1) and oleate (C18:1) had no such detrimental effects, appearing instead to effectively reverse palmitate-induced impairment of insulin-responsive GLUT4 recycling along with restoration of sortilin abundance by preventing aberrant PKC activation. On the other hand, shRNA-mediated reduction of sortilin in intact C2C12 myotubes inhibited insulin-induced GLUT4 recycling without dampening Akt phosphorylation. We found that the peroxisome proliferator-activated receptor ? agonist troglitazone prevented the palmitate-induced sortilin reduction and also ameliorated insulin-responsive GLUT4 recycling without altering the palmitate-evoked insults on signaling cascades; neither highly phosphorylated PKC states nor impaired insulin-responsive Akt phosphorylation was affected. Taken together, our data provide novel insights into the pathogenesis of PKC-dependent insulin resistance with respect to insulin-responsive GLUT4 translocation, which could occur not only through defects of insulin signaling but also via a reduction of sortilin, which directly controls trafficking/sorting of GLUT4 in skeletal muscle cells. In addition, our data suggest the insulin-sensitizing action of peroxisome proliferator-activated receptor ? agonists to be at least partially mediated through the restoration of proper GLUT4 trafficking/sorting events governed by sortilin. | lld:pubmed |
| pubmed-article:20805226 | pubmed:language | eng | lld:pubmed |
| pubmed-article:20805226 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20805226 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:20805226 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20805226 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20805226 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:20805226 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20805226 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20805226 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20805226 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20805226 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20805226 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20805226 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20805226 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20805226 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20805226 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20805226 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20805226 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:20805226 | pubmed:issn | 1083-351X | lld:pubmed |
| pubmed-article:20805226 | pubmed:author | pubmed-author:KanzakiMakoto... | lld:pubmed |
| pubmed-article:20805226 | pubmed:author | pubmed-author:MatsushitaShi... | lld:pubmed |
| pubmed-article:20805226 | pubmed:author | pubmed-author:TsuchiyaYoY | lld:pubmed |
| pubmed-article:20805226 | pubmed:author | pubmed-author:HatakeyamaHir... | lld:pubmed |
| pubmed-article:20805226 | pubmed:author | pubmed-author:EmotoNatsumiN | lld:pubmed |
| pubmed-article:20805226 | pubmed:author | pubmed-author:WagatsumaFumi... | lld:pubmed |
| pubmed-article:20805226 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:20805226 | pubmed:day | 5 | lld:pubmed |
| pubmed-article:20805226 | pubmed:volume | 285 | lld:pubmed |
| pubmed-article:20805226 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:20805226 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:20805226 | pubmed:pagination | 34371-81 | lld:pubmed |
| pubmed-article:20805226 | pubmed:dateRevised | 2011-11-17 | lld:pubmed |
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| pubmed-article:20805226 | pubmed:year | 2010 | lld:pubmed |
| pubmed-article:20805226 | pubmed:articleTitle | Palmitate-induced down-regulation of sortilin and impaired GLUT4 trafficking in C2C12 myotubes. | lld:pubmed |
| pubmed-article:20805226 | pubmed:affiliation | Graduate School of Biomedical Engineering, Tohoku University, Sendai 980-8575, Japan. | lld:pubmed |
| pubmed-article:20805226 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:20805226 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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