Strain Differences Determine the Suitability of Animal Models for Noninvasive In Vivo Beta Cell Mass Determination with Radiolabeled Exendin.
Strain Differences Determine the Suitability of Animal Models for Noninvasive In Vivo Beta Cell Mass Determination with Radiolabeled Exendin.
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DOI：
10.1007/s11307-016-0936-y
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发表时间：
2016-10
影响因子：
3.1
通讯作者：
Brom M
中科院分区：
文献类型：
--
作者：
Willekens SM;Joosten L;Boerman OC;Balhuizen A;Eizirik DL;Gotthardt M;Brom M
无创β细胞团（BCM）定量是了解糖尿病发生和进展的重要工具。[111]exendin是一种很有前途的体内β细胞成像剂，但由于缺乏明确定义的啮齿动物模型，示踪剂测试一直受到阻碍。比较了[111In]exendin在大鼠和小鼠体内的生物分布和胰腺摄取。在选定的模型中，使用四氧嘧啶诱导的β细胞损失模型来测定胰腺和其他器官中[111In]扩展蛋白蓄积量。采用RT-PCR和免疫组织化学分析GLP-1R的表达水平。即布朗挪威大鼠显示β细胞特异性示踪剂积累和有利的胰腺-背景比用于无创BCM测定。尽管GLP-1R在外分泌组织中的表达非常低，但小鼠在内分泌和外分泌胰腺中表现出受体介导的[111In]扩展蛋白摄取。与小鼠相比，大鼠在体内BCM测定中表现出更好的特征，被认为是更适合人类的模型。本文的在线版本（doi:10.1007/ s1107 -016-0936-y）包含补充材料，仅供授权用户使用。
Noninvasive beta cell mass (BCM) quantification is a crucial tool to understand diabetes development and progression. [111In]exendin is a promising agent for in vivo beta cell imaging, but tracer testing has been hampered by the lack of well-defined rodent models. Biodistribution and pancreatic uptake of [111In]exendin were compared in rats and mice. In selected models, the amount of [111In]exendin accumulation in the pancreas and other organs was determined using a model of alloxan-induced beta cell loss. GLP-1R expression levels were analyzed by RT-PCR and immunohistochemistry. Namely Brown Norway rats showed beta-cell-specific tracer accumulation and favorable pancreas-to-background ratios for noninvasive BCM determination. Mice displayed receptor-mediated [111In]exendin uptake in endocrine and exocrine pancreas, in spite of very low GLP-1R expression in exocrine tissue. Rats display better characteristics for in vivo BCM determination than mice and are suggested as a more adequate model for humans. The online version of this article (doi:10.1007/s11307-016-0936-y) contains supplementary material, which is available to authorized users.