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Diabetologia：Luseogliflozin通过激活胰岛素受体和IGF-1受体独立通路的体液因子促进细胞增殖

2020-04-12 MedSci原创 MedSci原创

体液因子；细胞增殖
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钠-葡萄糖共转运体2(SGLT2)抑制剂可阻止肾脏对葡萄糖的重吸收，以胰岛素依赖性的方式降低血糖水平。

钠-葡萄糖共转运体2(SGLT2)抑制剂可阻止肾脏对葡萄糖的重吸收，以胰岛素依赖性的方式降低血糖水平。我们之前报道了通过用胰岛素/IGF-1双受体抑制剂OSI-906治疗动物7天，建立了一个全身性抑制胰岛素和IGF-1靶向受体的小鼠模型。经OSI-906处理的小鼠表现出β细胞质量增加、肝脏脂肪沉积和脂肪组织萎缩，并伴有高胰岛素血症和高胰岛素血症。在本研究中，我们研究了SGLT2抑制剂luseogliflozin对OSI-906处理的小鼠的这些变化的影响。

研究人员使用vehicle、luseogliflozin、OSI-906或OSI-906 plus luseogliflozin对C57BL/6J雄性小鼠进行了7天的处理，并进行了表型分析，以确定细胞的数量和增殖情况。随后，在基因工程细胞、小鼠胰岛或人类胰岛中测试了血清衍生因子是否对细胞增殖有影响。

在经OSI -906处理的小鼠中，用luseogliflozin抑制SGLT2显著地改善了高血糖症，但没有改善高胰岛素血症。用luseogliflozin治疗小鼠的肝脏脱脂和脂肪组织萎缩没有改变。在OSI-906治疗的小鼠中，用luseogliflozin抑制SGLT2进一步增加了β细胞质量和增殖。Luseogliflozin上调了与M1(FoxM1)/polo样激酶1(PLK1)/centromere蛋白A(CENP-A)通路相关的基因表达。在Irs2敲除和Insr/IR敲除（βIRKO）β细胞与来自luseogliflozin-和OSI-906处理的小鼠的血清共培养中，β细胞增殖的增加被重述，但在β细胞中SGLT2抑制后，β细胞中的SGLT2抑制后，β细胞增殖的增加未得到重复。luseogliflozin-和OSI-906处理的小鼠中的循环因子都促进了小鼠肾小球和尸体人肾小球的β细胞增殖。

这些结果表明，luseogliflozin可以通过激活FoxM1/PLK1/CENP-A途径增加细胞增殖，而这种途径是通过一种与胰岛素/IGF-1受体无关的体液因子来实现的。

原始出处：

Kazuki Tajima， Tomoko Okuyama,Luseogliflozin increases beta cell proliferation through humoral factors that activate an insulin receptor- and IGF-1 receptor-independent pathway

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    2020-10-29 ms9608593228839890

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    2020-11-04 baoya

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    2020-04-25 qingrejiedu

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    2020-12-17 仁医06

    #IGF#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1639428, encodeId=4f1b163942877, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, 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 Oct 29 02:02:56 CST 2020, time=2020-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1750147, encodeId=386e1e501477a, content=<a href='/topic/show?id=be7c8385345' target=_blank style='color:#2F92EE;'>#胰岛#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, 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=Wed Nov 04 17:02:56 CST 2020, time=2020-11-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1761380, encodeId=a4161e6138023, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, 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=Mon Sep 14 23:02:56 CST 2020, time=2020-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1752413, encodeId=bd7d1e52413eb, content=<a href='/topic/show?id=20829492f8' target=_blank style='color:#2F92EE;'>#IGF-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9492, encryptionId=20829492f8, topicName=IGF-1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=deaa36532338, createdName=qingrejiedu, createdTime=Sat Apr 25 03:02:56 CST 2020, time=2020-04-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2039547, encodeId=e04f203954ea7, content=<a href='/topic/show?id=ca1294914d' target=_blank style='color:#2F92EE;'>#IGF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9491, encryptionId=ca1294914d, topicName=IGF)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Thu Dec 17 02:02:56 CST 2020, time=2020-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1540955, encodeId=4ef21540955a5, content=<a href='/topic/show?id=ba2ee78630b' target=_blank style='color:#2F92EE;'>#细胞增殖#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77863, encryptionId=ba2ee78630b, topicName=细胞增殖)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f58613291856, createdName=晓辰, createdTime=Tue Apr 14 12:02:56 CST 2020, time=2020-04-14, status=1, ipAttribution=)]
    2020-04-14 晓辰

    #细胞增殖#

    0