Diabetes:胰腺α细胞和β细胞增殖需要p300/CBP转录共激活。

2017-12-12 MedSci MedSci原创

p300(EP300)和CBP(CREBBP)转录共激活,具有组蛋白乙酰转移酶活性。已观察到多种β细胞转录因子可招募p300/CBP,因此,研究人员推测,该共激活剂可能对活体内β细胞发挥正常功能起着重要的作用。Chi Kin Wong等人猜测p300/CBP可促进胰腺的发育,维持胰腺的正常功能。研究人员利用缺乏p300/CBP的小鼠来验证上述猜测。胰腺缺乏p300或CBP的小鼠会出现胰腺分泌功能受

p300(EP300)和CBP(CREBBP)转录共激活,具有组蛋白乙酰转移酶活性。已观察到多种β细胞转录因子可招募p300/CBP,因此,研究人员推测,该共激活剂可能对活体内β细胞发挥正常功能起着重要的作用。

Chi Kin Wong等人猜测p300/CBP可促进胰腺的发育,维持胰腺的正常功能。

研究人员利用缺乏p300/CBP的小鼠来验证上述猜测。胰腺缺乏p300或CBP的小鼠会出现胰腺分泌功能受损、α/β细胞减少、胰岛素水平下降,表现为糖耐量异常。小鼠胰腺中仅表达p300或CBP的单拷贝时,上述表现型可加重。敲除胰腺内分泌祖细胞的p300,新生小鼠出现α/β细胞增殖障碍。完全敲除胰腺内分泌祖细胞的p300/CBP(即双纯合敲除),新生小鼠的胰腺不能形成α/β细胞团。

转录组学分析发现p300/CBP下调的基因与Hnf1α基因沉默的和Nkx2.2基因沉默的胰腺中下调的基因有显着的重复性。p300/CBP可显著影响Hnf1α基因沉默的胰腺的下调位点的H3K27的乙酰化。

综上所述,研究人员推测p300和CBP都是胰腺发育的限制性因子,可影响出生后的血糖稳态,功能有一定的重复性。

原始出处:

Chi Kin Wong,et al.The p300 and CBP Transcriptional Coactivators are Required for Beta Cell and Alpha Cell Proliferation.Diabetes  2017 Dec;  db170237.  https://doi.org/10.2337/db17-0237

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    2018-07-15 mjldent
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  6. 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  9. 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14 13:40:00 CST 2017, time=2017-12-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1618883, encodeId=4a931618883ae, content=<a href='/topic/show?id=007419239ca' target=_blank style='color:#2F92EE;'>#β细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19239, encryptionId=007419239ca, topicName=β细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b69919964433, createdName=ms24272190615788285182, createdTime=Thu Dec 14 13:40:00 CST 2017, time=2017-12-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=269082, encodeId=2833269082be, content=学习了.学习了., beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160914/IMG57D82E721DB581755.jpg, createdBy=4fc81933929, createdName=明天会更好!, createdTime=Wed Dec 13 10:20:16 CST 2017, time=2017-12-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=269009, encodeId=2ef9269009ea, content=阅读.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Wed Dec 13 06:00:05 CST 2017, time=2017-12-13, status=1, ipAttribution=)]
    2017-12-13 明天会更好!

    学习了.学习了.

    0

  10. 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createdBy=4fc81933929, createdName=明天会更好!, createdTime=Wed Dec 13 10:20:16 CST 2017, time=2017-12-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=269009, encodeId=2ef9269009ea, content=阅读.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Wed Dec 13 06:00:05 CST 2017, time=2017-12-13, status=1, ipAttribution=)]
    2017-12-13 刘煜

    阅读.谢谢分享

    0

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