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Nature Medicine:大脑或含二型糖尿病的新治疗靶点

2016-06-06 佚名 X-MOL

糖尿病一类常见的慢性疾病,如果不及时治疗会导致各种组织,例如眼、肾、神经等的慢性损害和功能障碍。糖尿病患者中的大部分属于二型糖尿病(type 2 diabetes mellitus, T2D),即非胰岛素依赖型糖尿病,患者体内产生胰岛素的能力并非完全丧失,但胰岛素的作用效果较差,可以通过某些口服药物刺激体内胰岛素的分泌,或者进行胰岛素注射治疗。但这些治疗方式都需每天给药来控制血糖,不能间断,过程繁


糖尿病一类常见的慢性疾病,如果不及时治疗会导致各种组织,例如眼、肾、神经等的慢性损害和功能障碍。糖尿病患者中的大部分属于二型糖尿病(type 2 diabetes mellitus, T2D),即非胰岛素依赖型糖尿病,患者体内产生胰岛素的能力并非完全丧失,但胰岛素的作用效果较差,可以通过某些口服药物刺激体内胰岛素的分泌,或者进行胰岛素注射治疗。但这些治疗方式都需每天给药来控制血糖,不能间断,过程繁琐甚至痛苦,或有低血糖及体重增加的副作用。X-MOL曾报道过不少新一代的糖尿病治疗方案,如长效的胰岛素衍生物、能实时监控血糖并给药的皮肤贴,这些研究大部分没有脱离传统的基于胰岛素的治疗策略。

越来越多的研究证据表明,大脑中成纤维细胞生长因子(fibroblast growth factor, FGF)受体的激活,能够引起强效的降糖响应,这似乎暗示着治疗二型糖尿病的另一个方向。美国华盛顿大学医学院Michael W Schwartz教授领导的团队基于之前的研究,在《Nature Medicine》刊文证明了大脑中FGF受体的确是治疗二型糖尿病的潜在药物靶标。他们在二型糖尿病小鼠和大鼠的脑室内注射FGF1,与其他FGF肽不同,FGF1可以激活所有的FGF受体亚型。结果让人吃惊,一次注射就能让小鼠和大鼠的血糖水平保持正常至少18个星期,而且没有低血糖及体重增加的副作用。(Central injection of fibroblast growth factor 1 induces sustained remission of diabetic hyperglycemia in rodents. Nat. Med., 2016, DOI: 10.1038/nm.4101)

以前的研究已经表明,FGF1在代谢中起着重要作用。血液中的FGF1的水平会“在你吃东西后上升,在你饥饿时下降”,美国萨克生物研究所的Ronald Evans说,他并没有参与此项研究。2014年,Evans和他的同事发现,给糖尿病小鼠注射FGF1(不是在脑室中),可以在两天左右的时间内让它们的血糖水平保持正常(Nature, 2014, 513, 436-439, DOI: 10.1038/nature13540)。

这篇论文的第一作者Jarrad M. Scarlett博士说,他们团队想确定FGF1是否通过大脑中的回路来起作用,要知道,负责调控饥饿和代谢的下丘脑中也含有FGF受体。为了找到答案,Schwartz和Scarlett等人将FGF1注射入二型糖尿病小鼠和大鼠的脑室内,所用剂量仅为3 µg,Evans等人所用剂量的1/10。尽管确切的机理仍然未知,脑室内注射FGF1增加了在肝脏和肌肉中的葡萄糖摄取。另一个重要的结果是,脑室内注射FGF1不会导致低血糖——这一胰岛素注射的常见副作用。

 

Evans说,这些结果和他实验室之前的结果都指向一个之前不为人所知的血糖调节机制,这很有希望成为治疗糖尿病的新方向。

除了要进一步研究大脑中的FGF1的作用机理,Scarlett说,他们团队也正在研究如何将FGF1输送到患者的大脑,毕竟脑部注射听起来太过于骇人。目前的一种可能是通过鼻腔喷雾的形式给药,他们将进行进一步的试验。

原始出处:

Jarrad M Scarlett,et al. Central injection of fibroblast growth factor 1 induces sustained remission of diabetic hyperglycemia in rodents. Nature Medicine. 2016.08 April.

Jae Myoung Suh,et al. Endocrinization of FGF1 produces a neomorphic and potent insulin sensitizer. Nature. 2014 18 September. 513, 436–439 .


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    2017-04-06 liye789132251
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    2016-09-21 1e10c84am36(暂无匿称)

    文章很好,非常有益

    0

  4. 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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=73801651090, createdName=1ddc978cm67(暂无匿称), createdTime=Thu Jun 09 08:55:00 CST 2016, time=2016-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1577476, encodeId=f42915e7476ab, content=<a href='/topic/show?id=cda91148004' target=_blank style='color:#2F92EE;'>#Medicine#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11480, encryptionId=cda91148004, topicName=Medicine)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=54cd16396700, createdName=ms1692212821629096, createdTime=Wed Jun 08 04:09:00 CST 2016, time=2016-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1606941, encodeId=a5a3160694184, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Wed Jun 08 04:09:00 CST 2016, time=2016-06-08, status=1, ipAttribution=)]
    2016-07-27 jeanqiuqiu
  5. 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style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Wed Jun 08 04:09:00 CST 2016, time=2016-06-08, status=1, ipAttribution=)]
    2016-09-15 舒心和人

    期待更深层次的研究

    0

  6. 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style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Wed Jun 08 04:09:00 CST 2016, time=2016-06-08, status=1, ipAttribution=)]
    2016-11-04 kalseyzl
  7. 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style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Wed Jun 08 04:09:00 CST 2016, time=2016-06-08, status=1, ipAttribution=)]
    2016-06-09 1ddc978cm67(暂无匿称)

    学习了,新思路

    0

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