Nat Commun:清除淀粉样蛋白低聚物可改善糖尿病

2021-01-08 MedSci原创 MedSci原创

最近,研究人员表明,其发现的一种自噬增强剂(MSL-7)可以减少人诱导多能干细胞衍生的β细胞(hiPSC-β细胞)中hIAPP寡聚体的积累,并减少寡聚体介导的β细胞凋亡。

虽然大多数关于糖尿病的基本发病机制的研究采用小鼠模型,人类糖尿病和小鼠糖尿病具有不同的几个关键特征。例如,小鼠模型和人类的胰岛结构和功能是不同的。这种差异可能是使用小鼠模型开发的抗糖尿病药物在人类临床试验中失败的原因。
糖尿病小鼠模型和人类糖尿病之间最有趣的差异之一是淀粉样蛋白在人类糖尿病患者的胰岛中沉积,但在小鼠模型中没有。在90%以上的人类糖尿病患者中观察到胰岛淀粉样蛋白沉积,但在小鼠糖尿病中却没有,这是由于胰岛淀粉样蛋白多肽(IAPP)的氨基酸序列不同造成的。已有的报导显示,表达人源hIAPP(hIAPP+小鼠)的转基因小鼠或hIAPP基因敲入小鼠中,当β细胞自噬缺失时,其低聚物或淀粉样蛋白积累明显增加,表明自噬在hIAPP低聚物或淀粉样蛋白的清除中至关重要。

 

 

自噬增强剂可能是一种针对人类糖尿病中淀粉样蛋白积累的治疗方式。最近,研究人员表明,其发现的一种自噬增强剂(MSL-7)可以减少人诱导多能干细胞衍生的β细胞(hiPSC-β细胞)中hIAPP寡聚体的积累,并减少寡聚体介导的β细胞凋亡。
在敲除MiTF/TFE家族成员,如Tfeb或Tfe3,的细胞中,MSL-7对hIAPP寡聚体积累和hIAPP寡聚体介导的β细胞死亡的保护作用显著降低。

 

 

MSL-7可改善高脂饮食下hIAPP+小鼠的葡萄糖耐受性和β细胞功能,同时减少hIAPP寡聚体/淀粉样蛋白的积累和β细胞凋亡。
MSL-7对hIAPP寡聚体介导的β细胞死亡和糖尿病发展的保护作用也因Tfeb的β细胞特异性敲除而显著降低。
这些结果表明,一种自噬增强剂可能对以胰岛淀粉样蛋白积累为特征的人类糖尿病具有治疗潜力。

 

原始出处:
Jinyoung Kim et al. An autophagy enhancer ameliorates diabetes of human IAPP-transgenic mice through clearance of amyloidogenic oligomer. Nature Communications 2021.

 

 

 

 

 

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createdName=zb1235672, createdTime=Fri Jan 08 23:22:58 CST 2021, time=2021-01-08, status=1, ipAttribution=)]
    2021-11-30 liye789132251
  2. 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    2021-07-11 124507acm01暂无昵称

    学习了

    0

  3. 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    2021-04-06 liuli5079
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createdBy=c1774999170, createdName=ms7405317358118777, createdTime=Sun Jan 10 14:11:30 CST 2021, time=2021-01-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=915101, encodeId=70d6915101a3, content=继续来学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200627/83a502bff6c14b759a7d0863b4068e7b/32ad40676056418ea58a94afac9c5b81.jpg, createdBy=6f475314305, createdName=水-晶, createdTime=Sat Jan 09 23:27:22 CST 2021, time=2021-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914831, encodeId=bcf09148318d, content=自噬热点话题, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=14a92089999, createdName=1781f416a9m, createdTime=Sat 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createdBy=59321624668, createdName=zb1235672, createdTime=Sat Jan 09 07:47:42 CST 2021, time=2021-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1043454, encodeId=f16f104345412, content=谢谢MedSci提供最新的资讯, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Sat Jan 09 02:11:30 CST 2021, time=2021-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914755, encodeId=76fc914e55fd, content=<a href='/topic/show?id=4f77e665253' target=_blank style='color:#2F92EE;'>#糖尿病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=127, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76652, encryptionId=4f77e665253, topicName=糖尿病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=59321624668, createdName=zb1235672, createdTime=Fri Jan 08 23:22:58 CST 2021, time=2021-01-08, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1884902, encodeId=5b0718849026d, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue Nov 30 10:11:30 CST 2021, time=2021-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=998623, encodeId=1dbc998623ba, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=9fa92477997, createdName=124507acm01暂无昵称, createdTime=Sun Jul 11 21:24:55 CST 2021, time=2021-07-11, status=1, ipAttribution=), 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createdBy=59321624668, createdName=zb1235672, createdTime=Sat Jan 09 07:47:42 CST 2021, time=2021-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1043454, encodeId=f16f104345412, content=谢谢MedSci提供最新的资讯, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Sat Jan 09 02:11:30 CST 2021, time=2021-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914755, encodeId=76fc914e55fd, content=<a href='/topic/show?id=4f77e665253' target=_blank style='color:#2F92EE;'>#糖尿病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=127, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76652, encryptionId=4f77e665253, topicName=糖尿病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=59321624668, createdName=zb1235672, createdTime=Fri Jan 08 23:22:58 CST 2021, time=2021-01-08, status=1, ipAttribution=)]
    2021-01-09 水-晶

    继续来学习了

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1884902, encodeId=5b0718849026d, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue Nov 30 10:11:30 CST 2021, time=2021-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=998623, encodeId=1dbc998623ba, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=9fa92477997, createdName=124507acm01暂无昵称, createdTime=Sun Jul 11 21:24:55 CST 2021, time=2021-07-11, status=1, ipAttribution=), 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Jan 09 10:50:16 CST 2021, time=2021-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914797, encodeId=396d914e971b, content=get, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210113/49ccb25556f441c0850bdefc3c8432be/5f80a486ed9f449ea166396944dbcc90.jpg, createdBy=b51f5435872, createdName=慕尔, createdTime=Sat Jan 09 08:04:03 CST 2021, time=2021-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914793, encodeId=d4df914e9396, content=<a href='/topic/show?id=4f77e665253' target=_blank style='color:#2F92EE;'>#糖尿病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=147, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76652, encryptionId=4f77e665253, topicName=糖尿病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=59321624668, createdName=zb1235672, createdTime=Sat Jan 09 07:47:42 CST 2021, time=2021-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1043454, encodeId=f16f104345412, content=谢谢MedSci提供最新的资讯, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Sat Jan 09 02:11:30 CST 2021, time=2021-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914755, encodeId=76fc914e55fd, content=<a href='/topic/show?id=4f77e665253' target=_blank style='color:#2F92EE;'>#糖尿病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=127, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76652, encryptionId=4f77e665253, topicName=糖尿病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=59321624668, createdName=zb1235672, createdTime=Fri Jan 08 23:22:58 CST 2021, time=2021-01-08, status=1, ipAttribution=)]
    2021-01-09 1781f416a9m

    自噬热点话题

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1884902, encodeId=5b0718849026d, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue Nov 30 10:11:30 CST 2021, time=2021-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=998623, encodeId=1dbc998623ba, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=9fa92477997, createdName=124507acm01暂无昵称, createdTime=Sun Jul 11 21:24:55 CST 2021, time=2021-07-11, status=1, ipAttribution=), 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Jan 09 10:50:16 CST 2021, time=2021-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914797, encodeId=396d914e971b, content=get, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210113/49ccb25556f441c0850bdefc3c8432be/5f80a486ed9f449ea166396944dbcc90.jpg, createdBy=b51f5435872, createdName=慕尔, createdTime=Sat Jan 09 08:04:03 CST 2021, time=2021-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914793, encodeId=d4df914e9396, content=<a href='/topic/show?id=4f77e665253' target=_blank style='color:#2F92EE;'>#糖尿病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=147, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76652, encryptionId=4f77e665253, topicName=糖尿病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=59321624668, createdName=zb1235672, createdTime=Sat Jan 09 07:47:42 CST 2021, time=2021-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1043454, encodeId=f16f104345412, content=谢谢MedSci提供最新的资讯, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Sat Jan 09 02:11:30 CST 2021, time=2021-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=914755, encodeId=76fc914e55fd, content=<a href='/topic/show?id=4f77e665253' target=_blank style='color:#2F92EE;'>#糖尿病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=127, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76652, encryptionId=4f77e665253, topicName=糖尿病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=59321624668, createdName=zb1235672, createdTime=Fri Jan 08 23:22:58 CST 2021, time=2021-01-08, status=1, ipAttribution=)]
    2021-01-09 慕尔

    get

    0

  8. 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  9. 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    2021-01-09 misszhang

    谢谢MedSci提供最新的资讯

    0

  10. 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