Linked Life Data

21323644

Source:http://linkedlifedata.com/resource/pubmed/id/21323644

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-7-5
pubmed:abstractText
Sustained over-supply of saturated non-esterified 'free' fatty acids has been shown to promote skeletal muscle insulin resistance, which may be driven, in part, by an increase in inflammatory signalling within this tissue. In the present manuscript we show that exposure of L6 myotubes to palmitate, a saturated fatty acid, induces activation of the NF-?B (nuclear factor ?B) pathway {based on increased IKK [I?B (inhibitory ?B) kinase] phosphorylation, I?B? loss and elevated interleukin-6 mRNA expression} and that this was associated with enhanced phosphorylation/activation of p38 MAPK (mitogen-activated protein kinase), JNK (c-Jun N-terminal kinase) and ERK (extracellular-signal-regulated kinase) as well as impaired insulin-dependent activation of PKB (protein kinase B)/Akt and glucose transport. NF-?B activation by palmitate was unaffected by pharmacological inhibition of p38 MAPK or JNK, but was suppressed significantly by inhibition of MEK (MAPK/ERK kinase)/ERK signalling. The importance of ERK with respect to downstream NF-?B signalling was underscored by the finding that PMA, a potent ERK activator, enhanced IKK phosphorylation. Strikingly, both palmitate- and PMA-induced activation of IKK/NF-?B were antagonized by AMPK (AMP-activated protein kinase) activators because of reduced ERK signalling. Although palmitate-induced activation of NF-?B was repressed by AMPK activation and by cellular overexpression of a mutated I?B? (S32A/S36A) super-repressor, this did not ameliorate the loss in insulin-stimulated PKB activation or glucose transport. Our results from the present study indicate that ERK plays a pivotal role in palmitate-induced activation of the IKK/NF-?B signalling axis and that AMPK can restrain the activity of this pro-inflammatory pathway. The finding that insulin resistance persists in myotubes in which NF-?B signalling has been repressed implies that palmitate and/or its lipid derivatives retain the capacity to impair insulin-regulated events independently of the increase in inflammatory signalling.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1470-8728
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
435
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
463-74
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Counter-modulation of fatty acid-induced pro-inflammatory nuclear factor ?B signalling in rat skeletal muscle cells by AMP-activated protein kinase.
pubmed:affiliation
Division of Cell Signalling and Immunology, Sir James Black Centre, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't