Strain Differences Determine the Suitability of Animal Models for Noninvasive In Vivo Beta Cell Mass Determination with Radiolabeled Exendin

菌株差异决定了动物模型是否适合用放射性标记的 Exendin 进行无创体内 β 细胞质量测定

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作者:Stefanie M A Willekens, Lieke Joosten, Otto C Boerman, Alexander Balhuizen, Decio L Eizirik, Martin Gotthardt, Maarten Brom

Conclusions

Rats display better characteristics for in vivo BCM determination than mice and are suggested as a more adequate model for humans.

Procedures

Biodistribution and pancreatic uptake of [(111)In]exendin were compared in rats and mice. In selected models, the amount of [(111)In]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.

Purpose

Noninvasive beta cell mass (BCM) quantification is a crucial tool to understand diabetes development and progression. [(111)In]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. Procedures: Biodistribution and pancreatic uptake of [(111)In]exendin were compared in rats and mice. In selected models, the amount of [(111)In]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.

Results

Namely Brown Norway rats showed beta-cell-specific tracer accumulation and favorable pancreas-to-background ratios for noninvasive BCM determination. Mice displayed receptor-mediated [(111)In]exendin uptake in endocrine and exocrine pancreas, in spite of very low GLP-1R expression in exocrine tissue. Conclusions: Rats display better characteristics for in vivo BCM determination than mice and are suggested as a more adequate model for humans.

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