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dc.contributor.authorValverde, Ángela M.-
dc.contributor.authorLorenzo, Margarita-
dc.contributor.authorNavarro, Paloma-
dc.contributor.authorMur, Cecilia-
dc.contributor.authorBenito, Manuel-
dc.identifierdoi: 10.1016/S0014-5793(00)01448-4-
dc.identifierissn: 0014-5793-
dc.identifiere-issn: 1873-3468-
dc.identifier.citationFEBS Letters 472(1): 153-158 (2000)-
dc.description.abstractIn the present study we have investigated the effect of increased serine/threonine phosphorylation of insulin receptor substrates-1 and -2 (IRS-1 and IRS-2) by okadaic acid pretreatment on brown adipocyte insulin signalling leading to glucose transport, an important metabolic effect of insulin in brown adipose tissue. Okadaic acid pretreatment before insulin stimulation decreased IRS-1 and IRS-2 tyrosine phosphorylation in parallel to a decrease in their sodium dodecyl sulfate-polyacrylamide gel electrophoresis mobility. IRS-1/IRS-2-associated p85α and phosphatidylinositol (PI) 3-kinase enzymatic activity were partly reduced in brown adipocytes pretreated with okadaic acid upon stimulation with insulin. Furthermore, insulin-induced glucose uptake was totally abolished by the inhibitor in parallel with a total inhibition of insulin-induced protein kinase C (PKC) ζ activity. However, activation of Akt/PKB or p70 S6 kinase (p70(s6k)) by insulin remained unaltered. Our results suggest that downstream of PI 3-kinase, insulin signalling diverges into at least two independent pathways through Akt/PKB and PKC ζ, the PKC ζ pathway contributing to glucose transport induced by insulin in fetal brown adipocytes.-
dc.description.sponsorshipThis work was supported by a grant PM98-0082 from the Ministerio de Educación y Cultura, Spain.-
dc.publisherJohn Wiley & Sons-
dc.publisherFederation of European Biochemical Societies-
dc.subjectInsulin resistance-
dc.subjectProtein kinase C ζ-
dc.subjectGlucose transport-
dc.subjectInsulin receptor substrate-
dc.subjectSerine/threonine phosphorylation-
dc.subjectOkadaic acid-
dc.subjectInsulin signaling-
dc.subjectIRS, insulin receptor substrate-
dc.subjectFCS, fetal calf serum-
dc.subjectPBS, phosphate buffered saline-
dc.subjectPI, phosphatidylinositol-
dc.titleOkadaic acid inhibits insulin-induced glucose transport in fetal brown adipocytes in an Akt-independent and protein kinase C ζ-dependent manner-
dc.description.versionPeer Reviewed-
dc.contributor.funderMinisterio de Educación y Cultura (España)-
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