Tasaki Yoshie, Taguchi Yusuke, Machida Takeo, Kobayashi Tetsuya
Division of Life Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-okubo, Sakura-ku, Saitama, Japan.
Congenit Anom (Kyoto). 2010 Sep;50(3):186-92. doi: 10.1111/j.1741-4520.2010.00287.x. Epub 2010 Jun 29.
Growth-retarded (grt) mice exhibit congenital hypothyroidism and a characteristic growth pause followed by delayed onset of pubertal growth. This pattern of growth has never been reported in any other animal model exhibiting hypothyroidism; therefore, the growth retardation observed in grt mice is unlikely to be explained completely by the low plasma thyroid hormone levels. As growth is closely related to nutrient metabolism, we investigated the relationship between the appearance of growth retardation and glucose utilization, which is the main component of nutrient metabolism, in the peripubertal stage of grt mice. The relative weights of the organs involved in nutrient digestion and absorption were abnormal in grt mice. The intraperitoneal glucose tolerance test (IGTT) showed impaired glucose tolerance in grt mice. Moreover, this symptom appeared in parallel with the progression of growth retardation in grt mice. The impaired blood glucose levels on the IGTT in grt mice were considered to be attributable to decreased plasma insulin levels rather than to impaired insulin sensitivity. The pattern of anti-insulin antibody staining on sections of pancreatic islets from grt mice was almost the same as that in the corresponding sections from normal mice. Insulin treatment accelerated the growth of peripubertal grt mice. These findings suggest that the appearance of growth retardation in grt mice might be partially attributable to a reduction in glucose metabolism and impairment of insulin secretion during the early period of growth.
生长迟缓（grt）小鼠表现出先天性甲状腺功能减退以及特征性的生长停滞，随后青春期生长延迟开始。这种生长模式在任何其他表现出甲状腺功能减退的动物模型中均未被报道；因此，在grt小鼠中观察到的生长迟缓不太可能完全由低血浆甲状腺激素水平来解释。由于生长与营养物质代谢密切相关，我们研究了在grt小鼠青春期前阶段生长迟缓的出现与葡萄糖利用之间的关系，葡萄糖利用是营养物质代谢的主要组成部分。grt小鼠中参与营养物质消化和吸收的器官相对重量异常。腹腔内葡萄糖耐量试验（IGTT）显示grt小鼠葡萄糖耐量受损。此外，这种症状与grt小鼠生长迟缓的进展同时出现。grt小鼠IGTT时血糖水平受损被认为是由于血浆胰岛素水平降低而非胰岛素敏感性受损所致。grt小鼠胰岛切片上抗胰岛素抗体染色模式与正常小鼠相应切片几乎相同。胰岛素治疗加速了青春期前grt小鼠的生长。这些发现表明，grt小鼠生长迟缓的出现可能部分归因于生长早期葡萄糖代谢减少和胰岛素分泌受损。
