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在移植环境中,升高的小鼠肝 betatrophin 表达并不会增加人β细胞的复制。

Elevated mouse hepatic betatrophin expression does not increase human β-cell replication in the transplant setting.

机构信息

Department of Genetics and Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.

出版信息

Diabetes. 2014 Apr;63(4):1283-8. doi: 10.2337/db13-1435. Epub 2013 Dec 18.

DOI:10.2337/db13-1435
PMID:24353178
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3964501/
Abstract

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.

摘要

最近发现的 betatrophin 是一种在胰岛素抵抗情况下由肝脏和白色脂肪组织分泌的蛋白质,它可以显著刺激小鼠胰岛素产生β细胞的复制,这为开发治疗糖尿病的新疗法带来了很高的期望。然而,目前尚不清楚 betatrophin 对人类β细胞的影响。在这里,我们使用胰岛素受体拮抗剂 S961 进行给药,该药物已被证明可增加 betatrophin 基因表达并刺激小鼠β细胞复制,以测试其对人类β细胞的作用。尽管小鼠β细胞在其正常位于胰腺的位置或移植到肾脏囊下时,β细胞 DNA 复制会急剧增加,但人类β细胞完全没有反应。这些结果使人们怀疑 betatrophin 是否可以作为治疗人类糖尿病的一种治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb32/3964501/77905f14792d/1283fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb32/3964501/59c272857e3b/1283fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb32/3964501/77905f14792d/1283fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb32/3964501/59c272857e3b/1283fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb32/3964501/77905f14792d/1283fig2.jpg

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本文引用的文献

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Cell. 2013 May 9;153(4):747-58. doi: 10.1016/j.cell.2013.04.008. Epub 2013 Apr 25.
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