File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: The adaptor protein APPL1 increases glycogen accumulation in rat skeletal muscle through activation of the PI3-kinase signalling pathway

TitleThe adaptor protein APPL1 increases glycogen accumulation in rat skeletal muscle through activation of the PI3-kinase signalling pathway
Authors
Issue Date2011
PublisherSociety for Endocrinology. The Journal's web site is located at http://joe.endocrinology-journals.org
Citation
Journal Of Endocrinology, 2011, v. 210 n. 1, p. 81-92 How to Cite?
AbstractAPPL1 is an adaptor protein that binds to both AKT and adiponectin receptors and is hypothesised to mediate the effects of adiponectin in activating downstream effectors such as AMP-activated protein kinase (AMPK). We aimed to establish whether APPL1 plays a physiological role in mediating glycogen accumulation and insulin sensitivity in muscle and the signalling pathways involved. In vivo electrotransfer of cDNA- and shRNA-expressing constructs was used to over-express or silence APPL1 for 1 week in single tibialis cranialis muscles of rats. Resulting changes in glucose and lipid metabolism and signalling pathway activation were investigated under basal conditions and in high-fat diet (HFD)- or chow-fed rats under hyperinsulinaemic- euglycaemic clamp conditions. APPL1 overexpression (OE) caused an increase in glycogen storage and insulin-stimulated glycogen synthesis in muscle, accompanied by a modest increase in glucose uptake. Glycogen synthesis during the clamp was reduced by HFD but normalised by APPL1 OE. These effects are likely explained by APPL1 OE-induced increase in basal and insulin-stimulated phosphorylation of IRS1, AKT, GSK3β and TBC1D4. On the contrary, APPL1 OE, such as HFD, reduced AMPK and acetyl-CoA carboxylase phosphorylation and PPARγ coactivator-1α and uncoupling protein 3 expression. Furthermore, APPL1 silencing caused complementary changes in glycogen storage and phosphorylation of AMPK and PI3-kinase pathway intermediates. Thus, APPL1 may provide a means for crosstalk between adiponectin and insulin signalling pathways, mediating the insulin-sensitising effects of adiponectin on muscle glucose disposal. These effects do not appear to require AMPK. Activation of signalling mediated via APPL1 may be beneficial in overcoming muscle insulin resistance. © 2011 Society for Endocrinology.
Persistent Identifierhttp://hdl.handle.net/10722/139455
ISSN
2015 Impact Factor: 4.498
2015 SCImago Journal Rankings: 1.910
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Health and Medical Research Council of Australia (NHMRC)481303
Royal Veterinary College (RVC) and Diabetes UK07/0003540
Wellcome Trust University
NHMRC
Funding Information:

This research was funded by the National Health and Medical Research Council of Australia (NHMRC, #481303), the Royal Veterinary College (RVC) and Diabetes UK (Small Grant #07/0003540). M E C is a Wellcome Trust University Award Fellow. N T is supported by a Career Development Award and E W K and G J C by Research Fellowships from the NHMRC.

References

 

DC FieldValueLanguage
dc.contributor.authorCleasby, MEen_HK
dc.contributor.authorLau, Qen_HK
dc.contributor.authorPolkinghorne, Een_HK
dc.contributor.authorPatel, SAen_HK
dc.contributor.authorLeslie, SJen_HK
dc.contributor.authorTurner, Nen_HK
dc.contributor.authorCooney, GJen_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorKraegen, EWen_HK
dc.date.accessioned2011-09-23T05:50:15Z-
dc.date.available2011-09-23T05:50:15Z-
dc.date.issued2011en_HK
dc.identifier.citationJournal Of Endocrinology, 2011, v. 210 n. 1, p. 81-92en_HK
dc.identifier.issn0022-0795en_HK
dc.identifier.urihttp://hdl.handle.net/10722/139455-
dc.description.abstractAPPL1 is an adaptor protein that binds to both AKT and adiponectin receptors and is hypothesised to mediate the effects of adiponectin in activating downstream effectors such as AMP-activated protein kinase (AMPK). We aimed to establish whether APPL1 plays a physiological role in mediating glycogen accumulation and insulin sensitivity in muscle and the signalling pathways involved. In vivo electrotransfer of cDNA- and shRNA-expressing constructs was used to over-express or silence APPL1 for 1 week in single tibialis cranialis muscles of rats. Resulting changes in glucose and lipid metabolism and signalling pathway activation were investigated under basal conditions and in high-fat diet (HFD)- or chow-fed rats under hyperinsulinaemic- euglycaemic clamp conditions. APPL1 overexpression (OE) caused an increase in glycogen storage and insulin-stimulated glycogen synthesis in muscle, accompanied by a modest increase in glucose uptake. Glycogen synthesis during the clamp was reduced by HFD but normalised by APPL1 OE. These effects are likely explained by APPL1 OE-induced increase in basal and insulin-stimulated phosphorylation of IRS1, AKT, GSK3β and TBC1D4. On the contrary, APPL1 OE, such as HFD, reduced AMPK and acetyl-CoA carboxylase phosphorylation and PPARγ coactivator-1α and uncoupling protein 3 expression. Furthermore, APPL1 silencing caused complementary changes in glycogen storage and phosphorylation of AMPK and PI3-kinase pathway intermediates. Thus, APPL1 may provide a means for crosstalk between adiponectin and insulin signalling pathways, mediating the insulin-sensitising effects of adiponectin on muscle glucose disposal. These effects do not appear to require AMPK. Activation of signalling mediated via APPL1 may be beneficial in overcoming muscle insulin resistance. © 2011 Society for Endocrinology.en_HK
dc.languageengen_US
dc.publisherSociety for Endocrinology. The Journal's web site is located at http://joe.endocrinology-journals.orgen_HK
dc.relation.ispartofJournal of Endocrinologyen_HK
dc.rights'Disclaimer. This is not the definitive version of record of this article. This manuscript has been accepted for publication in [insert name of journal], but the version presented here has not yet been copy edited, formatted or proofed. Consequently, the Society for Endocrinology accepts no responsibility for any errors or omissions it may contain. The definitive version is now freely available at [insert DOI link][insert year of publication] Society for Endocrinology.'-
dc.subject.meshCarrier Proteins - genetics - metabolism-
dc.subject.meshGlycogen - metabolism-
dc.subject.meshMuscle, Skeletal - metabolism-
dc.subject.meshNerve Tissue Proteins - genetics - metabolism-
dc.subject.meshPhosphatidylinositol 3-Kinase - metabolism-
dc.titleThe adaptor protein APPL1 increases glycogen accumulation in rat skeletal muscle through activation of the PI3-kinase signalling pathwayen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1479-6805 (Electronic) 0022-0795 (Linkin&volume=210&issue=1&spage=81&epage=92&date=2011&atitle=The+adaptor+protein+APPL1+increases+glycogen+accumulation+in+rat+skeletal+muscle+through+activation+of+the+PI3-kinase+signalling+pathwayen_US
dc.identifier.emailXu, A:amxu@hkucc.hku.hken_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1530/JOE-11-0039en_HK
dc.identifier.pmid21543456-
dc.identifier.pmcidPMC3114475-
dc.identifier.scopuseid_2-s2.0-79960297213en_HK
dc.identifier.hkuros194041en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79960297213&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume210en_HK
dc.identifier.issue1en_HK
dc.identifier.spage81en_HK
dc.identifier.epage92en_HK
dc.identifier.eissn1479-6805-
dc.identifier.isiWOS:000291633800010-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridCleasby, ME=6505770225en_HK
dc.identifier.scopusauthoridLau, Q=23489609600en_HK
dc.identifier.scopusauthoridPolkinghorne, E=23489919200en_HK
dc.identifier.scopusauthoridPatel, SA=7403902620en_HK
dc.identifier.scopusauthoridLeslie, SJ=35213456800en_HK
dc.identifier.scopusauthoridTurner, N=7202573171en_HK
dc.identifier.scopusauthoridCooney, GJ=7005169731en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridKraegen, EW=7006873142en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats