File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Skeletal muscle-specific overproduction of constitutively activated c-Jun N-terminal kinase (JNK) induces insulin resistance in mice

TitleSkeletal muscle-specific overproduction of constitutively activated c-Jun N-terminal kinase (JNK) induces insulin resistance in mice
Authors
Issue Date2012
PublisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00125/index.htm
Citation
Diabetologia, 2012, v. 55 n. 10, p. 2769-2778 How to Cite?
AbstractAIMS/HYPOTHESIS: Although skeletal muscle insulin resistance has been associated with activation of c-Jun N-terminal kinase (JNK), whether increased JNK activity causes insulin resistance in this organ is not clear. In this study we examined the metabolic consequences of isolated JNK phosphorylation in muscle tissue. METHODS: Plasmids containing genes encoding a wild-type JNK1 (WT-JNK) or a JNK1/JNKK2 fusion protein (rendering JNK constitutively active; CA-Jnk) were electroporated into one tibialis anterior (TA) muscle of C57Bl/6 mice, with the contralateral TA injected with an empty vector (CON) to serve as a within-animal control. RESULTS: Overproduction of WT-JNK resulted in a modest (~25%) increase in phosphorylation (Thr(183)/Tyr(185)) of JNK, but no differences were observed in Ser(307) phosphorylation of insulin receptor substrate 1 (IRS-1) or total IRS-1 protein, nor in insulin-stimulated glucose clearance into the TA muscle when comparing WT-JNK with CON. By contrast, overexpression of CA-Jnk, which markedly increased the phosphorylation of CA-JNK, also increased serine phosphorylation of IRS-1, markedly decreased total IRS-1 protein, and decreased insulin-stimulated phosphorylation of the insulin receptor (Tyr(1361)) and phosphorylation of Akt at (Ser(473) and Thr(308)) compared with CON. Moreover, overexpression of CA-Jnk decreased insulin-stimulated glucose clearance into the TA muscle compared with CON and these effects were observed without changes in intramuscular lipid species. CONCLUSIONS/INTERPRETATION: Constitutive activation of JNK in skeletal muscle impairs insulin signalling at the level of IRS-1 and Akt, a process which results in the disruption of normal glucose clearance into the muscle.
Persistent Identifierhttp://hdl.handle.net/10722/193194
ISSN
2023 Impact Factor: 8.4
2023 SCImago Journal Rankings: 3.355
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHenstridge, DC-
dc.contributor.authorBruce, CR-
dc.contributor.authorPang, CP-
dc.contributor.authorLancaster, GI-
dc.contributor.authorAllen, TL-
dc.contributor.authorEstevez, E-
dc.contributor.authorGardner, T-
dc.contributor.authorWeir, JM-
dc.contributor.authorMeikle, PJ-
dc.contributor.authorLam, KSL-
dc.contributor.authorXu, A-
dc.contributor.authorFujii, N-
dc.contributor.authorGoodyear, LJ-
dc.contributor.authorFebbraio, MA-
dc.date.accessioned2013-12-20T02:33:14Z-
dc.date.available2013-12-20T02:33:14Z-
dc.date.issued2012-
dc.identifier.citationDiabetologia, 2012, v. 55 n. 10, p. 2769-2778-
dc.identifier.issn0012-186X-
dc.identifier.urihttp://hdl.handle.net/10722/193194-
dc.description.abstractAIMS/HYPOTHESIS: Although skeletal muscle insulin resistance has been associated with activation of c-Jun N-terminal kinase (JNK), whether increased JNK activity causes insulin resistance in this organ is not clear. In this study we examined the metabolic consequences of isolated JNK phosphorylation in muscle tissue. METHODS: Plasmids containing genes encoding a wild-type JNK1 (WT-JNK) or a JNK1/JNKK2 fusion protein (rendering JNK constitutively active; CA-Jnk) were electroporated into one tibialis anterior (TA) muscle of C57Bl/6 mice, with the contralateral TA injected with an empty vector (CON) to serve as a within-animal control. RESULTS: Overproduction of WT-JNK resulted in a modest (~25%) increase in phosphorylation (Thr(183)/Tyr(185)) of JNK, but no differences were observed in Ser(307) phosphorylation of insulin receptor substrate 1 (IRS-1) or total IRS-1 protein, nor in insulin-stimulated glucose clearance into the TA muscle when comparing WT-JNK with CON. By contrast, overexpression of CA-Jnk, which markedly increased the phosphorylation of CA-JNK, also increased serine phosphorylation of IRS-1, markedly decreased total IRS-1 protein, and decreased insulin-stimulated phosphorylation of the insulin receptor (Tyr(1361)) and phosphorylation of Akt at (Ser(473) and Thr(308)) compared with CON. Moreover, overexpression of CA-Jnk decreased insulin-stimulated glucose clearance into the TA muscle compared with CON and these effects were observed without changes in intramuscular lipid species. CONCLUSIONS/INTERPRETATION: Constitutive activation of JNK in skeletal muscle impairs insulin signalling at the level of IRS-1 and Akt, a process which results in the disruption of normal glucose clearance into the muscle.-
dc.languageeng-
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00125/index.htm-
dc.relation.ispartofDiabetologia-
dc.subject.meshInsulin Resistance - physiology-
dc.subject.meshJNK Mitogen-Activated Protein Kinases - metabolism-
dc.subject.meshMuscle, Skeletal - metabolism-
dc.subject.meshPhosphorylation-
dc.subject.meshProto-Oncogene Proteins c-akt - metabolism-
dc.titleSkeletal muscle-specific overproduction of constitutively activated c-Jun N-terminal kinase (JNK) induces insulin resistance in mice-
dc.typeArticle-
dc.identifier.emailLam, KSL: ksllam@hku.hk-
dc.identifier.emailXu, A: amxu@hkucc.hku.hk-
dc.identifier.authorityLam, KSL=rp00343-
dc.identifier.authorityXu, A=rp00485-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1007/s00125-012-2652-8-
dc.identifier.pmid22832498-
dc.identifier.pmcidPMC3590919-
dc.identifier.scopuseid_2-s2.0-84866129230-
dc.identifier.hkuros226952-
dc.identifier.volume55-
dc.identifier.issue10-
dc.identifier.spage2769-
dc.identifier.epage2778-
dc.identifier.isiWOS:000308354600027-
dc.publisher.placeGermany-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats