Treatment options for gestational diabetes (GDM) are limited. In order to better understand mechanisms and improve treatments, appropriate animal models of GDM are crucial. Heterozygous db mice (db/+) present with glucose intolerance, insulin resistance, and increased weight gain during, but not prior to, pregnancy. This makes them an ideal model for GDM. However, several recent studies have reported an absence of GDM phenotype in their colony. We investigated several hypotheses for why the phenotype may be absent, with the aim of re-establishing it and preventing further resources being wasted on an ineffective model. Experiments were carried out across two laboratories in two countries (New Zealand and China), and were designed to assess type of control strain, diet, presence of the misty allele, and parity as potential contributors to the lost phenotype. While hyperleptinemia and pre-pregnancy weight gain were present in all db/+mice across the four studies, we found no consistent evidence of glucose intolerance or insulin resistance during pregnancy. In conclusion, we were unable to acquire the GDM phenotype in any of our experiments, and we recommend researchers do not use the db/+ mouse as a model of GDM unless they are certain the phenotype remains in their colony.

译文

妊娠糖尿病 (GDM) 的治疗选择有限。为了更好地了解机制和改善治疗,合适的GDM动物模型至关重要。杂合子db小鼠 (db/) 在怀孕期间 (但不在怀孕之前) 表现出葡萄糖耐受不良,胰岛素抵抗和体重增加。这使它们成为GDM的理想模型。然而,最近的几项研究报告了其菌落中不存在GDM表型。我们调查了为什么表型可能不存在的几种假设,目的是重新建立表型并防止在无效模型上浪费更多资源。实验是在两个国家 (新西兰和中国) 的两个实验室中进行的,旨在评估对照菌株的类型,饮食,雾状等位基因的存在以及作为失去表型的潜在贡献者的胎次。尽管在这四项研究中,所有db/小鼠中都存在高瘦素血症和孕前体重增加,但我们没有发现怀孕期间葡萄糖耐受不良或胰岛素抵抗的一致证据。总之,我们在任何实验中都无法获得GDM表型,我们建议研究人员不要将db/小鼠用作GDM的模型,除非他们确定表型仍保留在其菌落中。

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