엄성희 교수

(의과대학 분자세포생물학교실, SAIHST겸직)

 Impact Factor ('13) = 13.765      BRIC한빛사 논문

J Clin Invest. 2015 Jul 1;125(7):2736-47. doi: 10.1172/JCI77030. Epub 2015 Jun 15.

 

S6K1 controls pancreatic β cell size independently of intrauterine growth restriction.

Um SH, Sticker-Jantscheff M, Chau GC, Vintersten K, Mueller M, Gangloff YG, Adams RH, Spetz JF, Elghazi L, Pfluger PT, Pende M, Bernal-Mizrachi E, Tauler A, Tschöp MH, Thomas G, Kozma SC.

 

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.

 

PMID:26075820 [PubMed - indexed for MEDLINE]

PMCID: PMC4563673

 

(출처_PubMed)