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2015-07-01

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/177200

S6K1 controls pancreatic β cell size independently of intrauterine growth restriction

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Recurs relacionat

https://doi.org/10.1172/JCI77030

Resum

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.

Matèries

Retard del creixement intrauterí, Insulina, Enzimologia, Fisiologia, Proteïnes quinases

Matèries (anglès)

Fetal growth retardation, Insulin, Enzymology, Physiology, Protein kinases

Citació

Col·leccions

Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Bioquímica i Fisiologia)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

UM, Sung Hee, et al. S6K1 controls pancreatic β cell size independently of intrauterine growth restriction. Journal of Clinical Investigation. 2015. Vol. 125, num. 7, pags. 2736-2747. ISSN 0021-9738. [consulted: 11 of August of 2026]. Available at: https://hdl.handle.net/2445/177200

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