Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/177200
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 (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Bioquímica i Fisiologia)

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