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mTOR inhibition with rapamycin cause impaired insulin signalling and glucose uptake in human subcutaneous and omental adipocytes

2012Journal article Restricted access
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dc.contributor.authorPereira, Maria João
dc.contributor.authorPalming, Jenny
dc.contributor.authorRizell, Magnus
dc.contributor.authorAureliano, M.
dc.contributor.authorCarvalho, Eugénia
dc.contributor.authorSvensson, Maria K.
dc.contributor.authorEriksson, Jan W.
dc.date.accessioned2012-06-27T10:00:13Z
dc.date.available2012-06-27T10:00:13Z
dc.date.issued2012
dc.description.abstractRapamycin is an immunosuppressive agent used after organ transplantation, but its molecular effects on glucose metabolism needs further evaluation. We explored rapamycin effects on glucose uptake and insulin signalling proteins in adipocytes obtained via subcutaneous (n = 62) and omental (n = 10) fat biopsies in human donors. At therapeutic concentration (0.01 lM) rapamycin reduced basal and insulin-stimulated glucose uptake by 20–30%, after short-term (15 min) or long-term (20 h) culture of subcutaneous (n = 23 and n = 10) and omental adipocytes (n = 6 and n = 7). Rapamycin reduced PKB Ser473 and AS160 Thr642 phosphorylation, and IRS2 protein levels in subcutaneous adipocytes. Additionally, it reduced mTOR–raptor, mTOR–rictor and mTOR–Sin1 interactions, suggesting decreased mTORC1 and mTORC2 formation. Rapamycin also reduced IR Tyr1146 and IRS1 Ser307/Ser616/Ser636 phosphorylation, whereas no effects were observed on the insulin stimulated IRS1–Tyr and TSC2 Thr1462 phosphorylation. This is the first study to show that rapamycin reduces glucose uptake in human adipocytes through impaired insulin signalling and this may contribute to the development of insulin resistance associated with rapamycin therapy.por
dc.identifier.issn0303-7207
dc.identifier.urihttp://hdl.handle.net/10400.1/1326
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherElsevierpor
dc.subjectRapamycinpor
dc.subjectAdipocytespor
dc.titlemTOR inhibition with rapamycin cause impaired insulin signalling and glucose uptake in human subcutaneous and omental adipocytespor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage107por
oaire.citation.issue355por
oaire.citation.startPage96por
oaire.citation.titleMolecular and Cellular Endocrinologypor
person.familyNameAureliano
person.givenNameManuel
person.identifier584146
person.identifier.ciencia-idAA14-3490-DC5E
person.identifier.orcid0000-0003-4858-3201
person.identifier.ridI-3283-2012
person.identifier.scopus-author-id6603412860
rcaap.rightsrestrictedAccesspor
rcaap.typearticlepor
relation.isAuthorOfPublicationbb413661-7edd-4b57-8338-33889cfd05db
relation.isAuthorOfPublication.latestForDiscoverybb413661-7edd-4b57-8338-33889cfd05db

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