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Article

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Published version

Publication date

2015-07-01

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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/177200

S6K1 controls pancreatic β cell size independently of intrauterine growth restriction

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https://doi.org/10.1172/JCI77030

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.

Subject

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

Subject (English)

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

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

Citation

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: 10 of August of 2026]. Available at: https://hdl.handle.net/2445/177200

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