Division of Life Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-okubo, Sakura-ku, Saitama 338-8570, Japan.
J Endocrinol. 2010 Aug;206(2):195-204. doi: 10.1677/JOE-09-0465. Epub 2010 May 20.
The growth-retarded (grt) mouse shows thyroid dysfunction-related hyporesponsiveness to TSH. Thyroid hormone is a critical regulator of metabolism in many cells; thus, derangement of thyroid function affects many organs and systems. Experiments were conducted focusing on the function of the pancreatic islets in grt mice. We showed occurrence of a fasting hyperglycemia and a decreased plasma insulin level response to a glucose load in grt mice, despite normal insulin molecules being stored in secretory granules of pancreatic islets. We also demonstrated a reduction of insulin secretion in response to glucose administration from islets of grt mice in vitro, while the insulin release in response to KCl stimulation was comparable to that in normal mice, indicating that the isolated islets from grt mice have normal ATP-sensitive K(+) channels and postchannel activity. The mRNA expression levels of glucose transporter 2 and glucokinase in the islets of grt mice were similar to those in normal mice. Triiodothyronine administration to grt mice improved insulin secretion very slightly. On the other hand, mRNA for tyrosylprotein sulfotransferase 2 (Tpst2) was found to be expressed in the pancreatic islets of grt mice. Considering that Tpst2 is the responsible gene of grt mice, mutation of which is associated with a poor function of TSH receptor, the findings raise a possibility of involvement of factors including Tpst2 in the insulin hyposecretion in grt mice.
生长迟缓（grt）小鼠表现出甲状腺功能相关的 TSH 反应低下。甲状腺激素是许多细胞代谢的关键调节剂；因此，甲状腺功能紊乱会影响许多器官和系统。我们进行了专注于 grt 小鼠胰岛功能的实验。我们发现 grt 小鼠存在空腹高血糖和葡萄糖负荷后血浆胰岛素水平反应降低的现象，尽管胰岛中储存着正常的胰岛素分子。我们还证明了 grt 小鼠胰岛对葡萄糖刺激的胰岛素分泌减少，而对 KCl 刺激的胰岛素释放与正常小鼠相当，这表明 grt 小鼠分离的胰岛具有正常的 ATP 敏感性钾（K+）通道和通道后活性。grt 小鼠胰岛中的葡萄糖转运蛋白 2 和葡糖激酶的 mRNA 表达水平与正常小鼠相似。三碘甲状腺原氨酸（T3）给药对 grt 小鼠的胰岛素分泌仅有轻微改善。另一方面，在 grt 小鼠的胰岛中发现了酪氨酸蛋白硫酸转移酶 2（Tpst2）的 mRNA 表达。考虑到 Tpst2 是 grt 小鼠的致病基因，其突变与 TSH 受体功能不良有关，这些发现提示包括 Tpst2 在内的因素可能参与了 grt 小鼠的胰岛素分泌不足。
