糖尿病相关最新一篇文章

大猪小猪落玉盘

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- b% `" p  w, S$ C4 mIntrauterine growth retardation (IUGR) has been linked to the onset of diseases in adulthood, including type
& I9 m, j, D' R) h7 a: |" P6 L2 diabetes, and has been proposed to result from altered gene regulation patterns due to epigenetic modifications# a/ H" w" E# R# r9 v; K* f) S
of developmental genes. To determine whether epigenetic modifications may play a role in the development1 m) z; u! H; h
of adult diabetes following IUGR, we used a rodent model of IUGR that expresses lower levels of Pdx1, a
0 t/ f0 ]) z/ B: P$ q+ @% \9 npancreatic and duodenal homeobox 1 transcription factor critical for β cell function and development, which
8 n8 i  S& {- W6 k$ |, Zdevelops diabetes in adulthood. We found that expression of Pdx1 was permanently reduced in IUGR β cells/ T1 g% @9 z3 m
and underwent epigenetic modifications throughout development. The fetal IUGR state was characterized by
' v0 X! Q$ }, }( @& Closs of USF-1 binding at the proximal promoter of Pdx1, recruitment of the histone deacetylase 1 (HDAC1) and
% C1 A' K$ i8 b; _! o, Ethe corepressor Sin3A, and deacetylation of histones H3 and H4. Following birth, histone 3 lysine 4 (H3K4)
' Y0 Y' k* {: i5 {2 n7 ewas demethylated and histone 3 lysine 9 (H3K9) was methylated. During the neonatal period, these epigenetic5 O, ?: Y+ M) V
changes and the reduction in Pdx1 expression could be reversed by HDAC inhibition. After the onset of diabetes
2 E2 M& y/ g% {in adulthood, the CpG island in the proximal promoter was methylated, resulting in permanent silencing# r2 D! d1 a7 r9 f
of the Pdx1 locus. These results provide insight into the development of type 2 diabetes following IUGR and we
& X1 D5 t! Z& @# |, ?believe they are the first to describe the ontogeny of chromatin remodeling in vivo from the fetus to the onset
3 f3 E! ~% {- @of disease in adulthood.
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cdcliwei

Well done!

xiaomao_zhoubo

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jimzhua

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missyoudad

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