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Title: | S6K1 controls pancreatic β cell size independently of intrauterine growth restriction |
Author: | Um, Sung Hee Sticker-Jantscheff, Melanie Chau, Gia Cac Vintersten, Kristina Mueller, Matthias Gangloff, Yann-Gael Adams, Ralf H. Spetz, Jean-François Elghazi, Lynda Pfluger, Paul T. Pende, Mario Bernal-Mizrachi, Ernesto Tauler Girona, Albert Tschöp, Matthias H. Thomas, George Kozma, Sara C. |
Keywords: | Retard del creixement intrauterí Insulina Enzimologia Fisiologia Proteïnes quinases Fetal growth retardation Insulin Enzymology Physiology Protein kinases |
Issue Date: | 1-Jul-2015 |
Publisher: | American Society for Clinical Investigation |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1172/JCI77030 |
It is part of: | Journal of Clinical Investigation, 2015, vol. 125, num. 7, p. 2736-2747 |
URI: | http://hdl.handle.net/2445/177200 |
Related resource: | https://doi.org/10.1172/JCI77030 |
ISSN: | 0021-9738 |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Bioquímica i Fisiologia) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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