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Diabetologia:GLP-1联合雌激素,可以阻止胰岛B细胞功能衰竭

2015-01-12 angletears 译 MedSci原创

之前有研究证明,雌激素有明显改善B细胞功能,降低血糖的作用。因此,近来开始研发GLP-1—雌激素结合物来治疗T2DM,此结合物可以将雌激素特异性的送至表达GLP-1受体的细胞,通过雌激素增加GLP-1对胰岛B细胞的保护作用。最近一篇研究就,比较了GLP-1和GLP-1—雌激素结合物在糖毒性环境中对胰岛B细胞的保护作用。研究中随机选取两组新西兰肥胖(NZO)小鼠,分别给予每日GLP-1和GLP-1—

之前有研究证明,雌激素有明显改善B细胞功能,降低血糖的作用。因此,近来开始研发GLP-1—雌激素结合物来治疗T2DM,此结合物可以将雌激素特异性的送至表达GLP-1受体的细胞,通过雌激素增加GLP-1对胰岛B细胞的保护作用。最近一篇研究就,比较了GLP-1和GLP-1—雌激素结合物在糖毒性环境中对胰岛B细胞的保护作用。




研究中随机选取两组新西兰肥胖(NZO)小鼠,分别给予每日GLP-1和GLP-1—雌激素结合物皮下注射。随后,评估小鼠的能量代谢状态,并检测B细胞的完整性。为了阐明,GLP-1—雌激素结合物的靶向作用,对编码雌激素的基因进行转录分析,同时对胰岛细胞进行微阵列分析。

结果,与GLP-1相比,GLP-1—雌激素结合物可以显著抑制进食,明显降低体重,维持正常血糖状态,提高葡萄糖耐量,并且增强对B细胞的保护作用。对下丘脑的mRNA进行分析,发现阿片-促黑素细胞皮质素原和瘦素受体的表达增加。接受GLP-1—雌激素结合物治疗的小鼠肝脏,脂源性基因的表达减弱,而且,甘油三酯的水平降低。在胰岛细胞中,GLP-1—雌激素结合物改变了其mRNA的表达,以抵制糖尿病的发生。但是,传统的雌激素编码基因也是一样,表现为间接的胰岛B细胞的保护作用。

在NZO小鼠中,GLP-1—雌激素结合物可以通过减少摄食,有效抵制碳水化合物诱发的胰岛B细胞衰竭。就这一点而言,将雌激素靶向送至下丘脑(通过GLP-1—雌激素结合物),与单用的GLP-1相比,前者可以产生更强的抗食欲作用。

最后,研究者认为,雌激素联合GLP-1,比起单用GLP-1来说,对饮食诱导的糖尿病表现出更明显的保护作用。在NZO小鼠中,这种保护机制是因其减弱下丘脑的进食中枢的信号传递,从而改善机体的糖耐量和胰岛素敏感性。因此,激素混合物,比如GLP-1—雌激素结合物可能会成为,研发更高效的治疗T2DM新型药物的基础。

原始出处:

Schwenk RW1, Baumeier C, Finan B, Kluth O, Brauer C, Joost H, DiMarchi RD, Tschöp MH, Schürmann A.GLP-1-oestrogen attenuates hyperphagia and protects from beta cell failure in diabetes-prone New Zealand obese (NZO) mice.Diabetologia. 2014 Dec 20. [Epub ahead of print]

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    2015-07-18 baoya
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    2015-01-14 yibei
  7. [GetPortalCommentsPageByObjectIdResponse(id=1749526, encodeId=55fd1e49526e6, content=<a href='/topic/show?id=be7c8385345' target=_blank style='color:#2F92EE;'>#胰岛#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83853, encryptionId=be7c8385345, topicName=胰岛)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a7a536274692, createdName=baoya, createdTime=Sat Jul 18 05:19:00 CST 2015, time=2015-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2055451, encodeId=a097205545160, content=<a href='/topic/show?id=8de28385453' target=_blank style='color:#2F92EE;'>#胰岛B细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83854, encryptionId=8de28385453, topicName=胰岛B细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=医者仁心, createdTime=Tue May 26 20:19:00 CST 2015, time=2015-05-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1637020, encodeId=e081163e02082, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5916, encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Thu Jul 09 00:19:00 CST 2015, time=2015-07-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1759519, encodeId=37ce1e59519e2, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Sun Mar 15 19:19:00 CST 2015, time=2015-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1273162, encodeId=180112e3162e7, content=<a href='/topic/show?id=310d383ef5' target=_blank style='color:#2F92EE;'>#B细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3837, encryptionId=310d383ef5, topicName=B细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6eba113, createdName=xiaoyeshuang, createdTime=Wed Jan 14 04:19:00 CST 2015, time=2015-01-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1422688, encodeId=ec181422688fd, content=<a href='/topic/show?id=54fa80e701' target=_blank style='color:#2F92EE;'>#GLP-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8077, encryptionId=54fa80e701, topicName=GLP-1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f8f23732777, createdName=yibei, createdTime=Wed Jan 14 04:19:00 CST 2015, time=2015-01-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1586780, encodeId=3c431586e80f0, content=<a href='/topic/show?id=a6d1e7821de' target=_blank style='color:#2F92EE;'>#细胞功能#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77821, encryptionId=a6d1e7821de, topicName=细胞功能)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2ec517387980, createdName=般若傻瓜, createdTime=Wed Jan 14 04:19:00 CST 2015, time=2015-01-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=14287, encodeId=a63a1428e1e, content=这一点提示GLP-1或DDP-4制剂应该早用?, beContent=null, objectType=article, channel=null, level=null, likeNumber=139, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=lifefamily, createdTime=Tue Jan 13 22:46:00 CST 2015, time=2015-01-13, status=1, ipAttribution=)]
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    2015-01-13 lifefamily

    这一点提示GLP-1或DDP-4制剂应该早用?

    0

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