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http://hdl.handle.net/2445/177200
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DC Field | Value | Language |
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dc.contributor.author | Um, Sung Hee | - |
dc.contributor.author | Sticker-Jantscheff, Melanie | - |
dc.contributor.author | Chau, Gia Cac | - |
dc.contributor.author | Vintersten, Kristina | - |
dc.contributor.author | Mueller, Matthias | - |
dc.contributor.author | Gangloff, Yann-Gael | - |
dc.contributor.author | Adams, Ralf H. | - |
dc.contributor.author | Spetz, Jean-François | - |
dc.contributor.author | Elghazi, Lynda | - |
dc.contributor.author | Pfluger, Paul T. | - |
dc.contributor.author | Pende, Mario | - |
dc.contributor.author | Bernal-Mizrachi, Ernesto | - |
dc.contributor.author | Tauler Girona, Albert | - |
dc.contributor.author | Tschöp, Matthias H. | - |
dc.contributor.author | Thomas, George | - |
dc.contributor.author | Kozma, Sara C. | - |
dc.date.accessioned | 2021-05-11T14:32:50Z | - |
dc.date.available | 2021-05-11T14:32:50Z | - |
dc.date.issued | 2015-07-01 | - |
dc.identifier.issn | 0021-9738 | - |
dc.identifier.uri | http://hdl.handle.net/2445/177200 | - |
dc.description.abstract | Type 2 diabetes mellitus (T2DM) is a worldwide heath problem that is characterized by insulin resistance and the eventual loss of β cell function. As recent studies have shown that loss of ribosomal protein (RP) S6 kinase 1 (S6K1) increases systemic insulin sensitivity, S6K1 inhibitors are being pursued as potential agents for improving insulin resistance. Here we found that S6K1 deficiency in mice also leads to decreased β cell growth, intrauterine growth restriction (IUGR), and impaired placental development. IUGR is a common complication of human pregnancy that limits the supply of oxygen and nutrients to the developing fetus, leading to diminished embryonic β cell growth and the onset of T2DM later in life. However, restoration of placental development and the rescue of IUGR by tetraploid embryo complementation did not restore β cell size or insulin levels in S6K1-/- embryos, suggesting that loss of S6K1 leads to an intrinsic β cell lesion. Consistent with this hypothesis, reexpression of S6K1 in β cells of S6K1-/- mice restored embryonic β cell size, insulin levels, glucose tolerance, and RPS6 phosphorylation, without rescuing IUGR. Together, these data suggest that a nutrient-mediated reduction in intrinsic β cell S6K1 signaling, rather than IUGR, during fetal development may underlie reduced β cell growth and eventual development of T2DM later in life. | - |
dc.format.extent | 12 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | American Society for Clinical Investigation | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1172/JCI77030 | - |
dc.relation.ispartof | Journal of Clinical Investigation, 2015, vol. 125, num. 7, p. 2736-2747 | - |
dc.relation.uri | https://doi.org/10.1172/JCI77030 | - |
dc.rights | (c) American Society for Clinical Investigation, 2015 | - |
dc.source | Articles publicats en revistes (Ciències Fisiològiques) | - |
dc.subject.classification | Retard del creixement intrauterí | - |
dc.subject.classification | Insulina | - |
dc.subject.classification | Enzimologia | - |
dc.subject.classification | Fisiologia | - |
dc.subject.classification | Proteïnes quinases | - |
dc.subject.other | Fetal growth retardation | - |
dc.subject.other | Insulin | - |
dc.subject.other | Enzymology | - |
dc.subject.other | Physiology | - |
dc.subject.other | Protein kinases | - |
dc.title | S6K1 controls pancreatic β cell size independently of intrauterine growth restriction | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 656783 | - |
dc.date.updated | 2021-05-11T14:32:50Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 26075820 | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Bioquímica i Fisiologia) |
Files in This Item:
File | Description | Size | Format | |
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656783.pdf | 5.26 MB | Adobe PDF | View/Open |
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