Vis enkel innførsel

dc.contributor.authorStuenæs, Jorid T.
dc.contributor.authorBolling, Astrid
dc.contributor.authorIngvaldsen, Ada
dc.contributor.authorRommundstad, Camilla
dc.contributor.authorSudar, Emina
dc.contributor.authorLin, Fang-Chin
dc.contributor.authorLai, Yu-Chiang
dc.contributor.authorJensen, Jørgen
dc.date.accessioned2011-04-07T09:56:13Z
dc.date.available2011-04-07T09:56:13Z
dc.date.issued2010-03-23
dc.identifierSeksjon for fysisk prestasjonsevne / Department of Physical Performance
dc.identifier.citationBritish Journal of Pharmacology. 2010, 160(1), 116-129en_US
dc.identifier.issn0007-1188
dc.identifier.urihttp://hdl.handle.net/11250/170805
dc.descriptionI Brage finner du siste tekst-versjon av artikkelen, og den kan inneholde ubetydelige forskjeller fra forlagets pdf-versjon. Forlagets pdf-versjon finner du på onlinelibrary.wiley.com: http://dx.doi.org/10.1111/j.1476-5381.2010.00677.x / In Brage you'll find the final text version of the article, and it may contain insignificant differences from the journal's pdf version. The original publication is available at onlinelibrary.wiley.com: http://dx.doi.org/10.1111/j.1476-5381.2010.00677.xen_US
dc.description.abstractBACKGROUND AND PURPOSE: Genetic approaches have documented protein kinase B (PKB) as a pivotal regulator of heart function. Insulin strongly activates PKB, whereas adrenaline is not considered a major physiological regulator of PKB in heart. In skeletal muscles, however, adrenaline potentiates insulin-stimulated PKB activation without having effect in the absence of insulin. The purpose of the present study was to investigate the interaction between insulin and beta-adrenergic stimulation in regulation of PKB phosphorylation. EXPERIMENTAL APPROACH: Cardiomyocytes were isolated from adult rats by collagenase, and incubated with insulin, isoprenaline, and other compounds. Protein phosphorylation was evaluated by Western blot and phospho-specific antibodies. KEY RESULTS: Isoprenaline increased insulin-stimulated PKB Ser(473) and Thr(308) phosphorylation more than threefold in cardiomyocytes. Isoprenaline alone did not increase PKB phosphorylation. Isoprenaline also increased insulin-stimulated GSK-3beta Ser(9) phosphorylation approximately twofold, supporting that PKB phosphorylation increased kinase activity. Dobutamine (beta(1)-agonist) increased insulin-stimulated PKB phosphorylation as effectively as isoprenaline (more than threefold), whereas salbutamol (beta(2)-agonist) only potentiated insulin-stimulated PKB phosphorylation by approximately 80%. Dobutamine, but not salbutamol, increased phospholamban Ser(16) phosphorylation and glycogen phosphorylase activation (PKA-mediated effects). Furthermore, the cAMP analogue that activates PKA (dibutyryl-cAMP and N(6)-benzoyl-cAMP) increased insulin-stimulated PKB phosphorylation by more than threefold without effect alone. The Epac-specific activator 8-(4-chlorophenylthio)-2'-O-methyl-cAMP (007) increased insulin-stimulated PKB phosphorylation by approximately 50%. Db-cAMP and N(6)-benzoyl-cAMP, but not 007, increased phospholamban Ser(16) phosphorylation. CONCLUSIONS AND IMPLICATIONS: beta-adrenoceptors are strong regulators of PKB phosphorylation via cAMP and PKA when insulin is present. We hypothesize that PKB mediates important signalling in the heart during beta-adrenergic receptors stimulation.en_US
dc.language.isoengen_US
dc.publisherWileyen_US
dc.subjectadrenergic beta-agonistsen_US
dc.subjectanimalsen_US
dc.subjectcalcium-binding proteinsen_US
dc.subjectcyclic AMPen_US
dc.subjectdobutamineen_US
dc.subjectdrug synergismen_US
dc.subjectenzyme activationen_US
dc.subjectglycogen phosphorylaseen_US
dc.subjectinsulinen_US
dc.subjectisoproterenolen_US
dc.subjectmyocytes, cardiacen_US
dc.subjectphosphorylationen_US
dc.subjectproto-oncogene proteins c-akten_US
dc.subjectratsen_US
dc.subjectreceptors, adrenergic, betaen_US
dc.titleBeta-Adrenoceptor stimulation potentiates insulin-stimulated PKB phosphorylation in rat cardiomyocytes via cAMP and PKAen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.subject.nsiVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.source.pagenumber116-129en_US


Tilhørende fil(er)

Thumbnail

Denne innførselen finnes i følgende samling(er)

Vis enkel innførsel