糖尿病相关最新一篇文章

大猪小猪落玉盘

3 x' K  ?- d0 }& R- @5 n6 `- L

# }0 \) e/ l0 X/ x* w+ `Intrauterine growth retardation (IUGR) has been linked to the onset of diseases in adulthood, including type9 s8 y7 G  S% F( ~
2 diabetes, and has been proposed to result from altered gene regulation patterns due to epigenetic modifications
8 E8 B& v# z. p+ cof developmental genes. To determine whether epigenetic modifications may play a role in the development8 I% K+ W; w( D( `- U
of adult diabetes following IUGR, we used a rodent model of IUGR that expresses lower levels of Pdx1, a
* ?9 p5 X/ N7 U  ?; Ipancreatic and duodenal homeobox 1 transcription factor critical for β cell function and development, which
8 p) B2 Q0 x0 d! }& t1 c; ydevelops diabetes in adulthood. We found that expression of Pdx1 was permanently reduced in IUGR β cells
3 Y6 w* r2 [. W0 C, J- t/ y4 Pand underwent epigenetic modifications throughout development. The fetal IUGR state was characterized by* B( n( Z+ ?7 H! E" L- }/ }8 x
loss of USF-1 binding at the proximal promoter of Pdx1, recruitment of the histone deacetylase 1 (HDAC1) and
' l+ O& H/ Y+ R$ |+ s& X0 K( Sthe corepressor Sin3A, and deacetylation of histones H3 and H4. Following birth, histone 3 lysine 4 (H3K4)+ d7 X) @! Q9 F- W
was demethylated and histone 3 lysine 9 (H3K9) was methylated. During the neonatal period, these epigenetic+ g' Z: w7 T' x0 [+ M$ a9 c3 q" d
changes and the reduction in Pdx1 expression could be reversed by HDAC inhibition. After the onset of diabetes
. C* L4 V# F+ }6 ]% R3 W) }in adulthood, the CpG island in the proximal promoter was methylated, resulting in permanent silencing! j# M$ b4 M6 ^# r& L
of the Pdx1 locus. These results provide insight into the development of type 2 diabetes following IUGR and we
- H% c2 ^8 \6 [  r' P6 Cbelieve they are the first to describe the ontogeny of chromatin remodeling in vivo from the fetus to the onset" [0 R1 Q5 [0 j8 ]& X5 o
of disease in adulthood.
# Z( V. a0 q4 j/ P' E交流中升华进步！
" V1 I# X* D! e% v
" H7 \( z8 u0 k4 g

cdcliwei

Well done!

xiaomao_zhoubo

支持

jimzhua

谢谢

missyoudad

谢谢分享

w1986725

看看

荷荷

看看