Elevated mouse hepatic betatrophin expression does not increase human β-cell replication in the transplant setting.
Elevated mouse hepatic betatrophin expression does not increase human β-cell replication in the transplant setting.
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DOI：
10.2337/db13-1435
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发表时间：
2014-04
期刊：
影响因子：
7.7
通讯作者：
Kaestner KH
中科院分区：
文献类型：
--
作者：
Jiao Y;Le Lay J;Yu M;Naji A;Kaestner KH
betatrophin是一种在胰岛素抵抗状态下由肝脏和白色脂肪组织分泌的蛋白质，可以显著刺激小鼠产生胰岛素的β细胞的复制。最近发现的betatrophin使人们对快速开发一种治疗糖尿病的新方法寄予了厚望。然而，目前，betatrophin对人β细胞的作用尚不清楚。在这里，我们使用胰岛素受体拮抗剂S961来测试其对人类β细胞的影响，S961可以增加β萎缩素基因表达并刺激小鼠β细胞复制。尽管小鼠β细胞在胰腺的正常位置或移植到肾包膜下时，对β细胞DNA复制的急剧增加作出反应，但人类β细胞完全没有反应。这些结果对betatrophin是否可以作为治疗人类糖尿病的治疗方法提出了质疑。
The recent discovery of betatrophin, a protein secreted by the liver and white adipose tissue in conditions of insulin resistance and shown to dramatically stimulate replication of mouse insulin-producing β-cells, has raised high hopes for the rapid development of a novel therapeutic approach for the treatment of diabetes. At present, however, the effects of betatrophin on human β-cells are not known. Here we use administration of the insulin receptor antagonist S961, shown to increase betatrophin gene expression and stimulate β-cell replication in mice, to test its effect on human β-cells. Although mouse β-cells, in their normal location in the pancreas or when transplanted under the kidney capsule, respond with a dramatic increase in β-cell DNA replication, human β-cells are completely unresponsive. These results put into question whether betatrophin can be developed as a therapeutic approach for treating human diabetes.
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影响因子：
10.5
作者：
Gupta, Rana K.;Gao, Nan;Kaestner, Klaus H.
通讯作者：
Kaestner, Klaus H.
影响因子：
29
作者：
Porat, Shay;Weinberg-Corem, Noa;Dor, Yuval
通讯作者：
Dor, Yuval
DOI：
10.1073/pnas.1217552109
发表时间：
2012-11-27
影响因子：
11.1
作者：
Quagliarini, Fabiana;Wang, Yan;Hobbs, Helen H.
通讯作者：
Hobbs, Helen H.
影响因子：
64.8
作者：
Dor, Y;Brown, J;Melton, DA
通讯作者：
Melton, DA
影响因子：
64.5
作者：
Yi P;Park JS;Melton DA
通讯作者：
Melton DA