Momose Kazuko, Nunomiya Shin, Nakata Masanori, Yada Toshihiko, Kikuchi Motoshi, Yashiro Takashi
Department of Anesthesiology and Intensive Care Medicine, Jichi Medical University School of Medicine, Shimotsuke-shi, Tochigi 329-0433, Japan.
Med Mol Morphol. 2006 Sep;39(3):146-53. doi: 10.1007/s00795-006-0324-9.
The Goto-Kakizaki (GK) rat offers a genetic model of type 2 diabetes and displays profoundly defective insulin secretion leading to basal hyperglycemia. This animal is widely used for studying type 2 diabetes. However, the morphological characteristics of the pancreatic islets of Langerhans in GK rats are not fully understood. The present study sought to clarify this issue using immunohistochemical and electron microscopic techniques. GK rats were killed at 7, 14, 21, and 35 weeks of age. Structural islet changes were not observed at 7 weeks old. At 14 and 21 weeks of age, GK rats displayed histopathological islet changes. The general shape of islets became irregular, and immunoreaction of beta-cells against antiinsulin appeared diffusely weakened. Electron microscopy revealed that the numbers of so-called beta-granules decreased and the numbers of immature granules increased. The Golgi apparatus of beta-cells was developed and the cisternae of rough endoplasmic reticulum were often dilated, indicating hyperfunction of the cells. However, at 35 weeks old, immunoreactivities of dispersed beta-cells into the exocrine portion recovered, and numbers of secretory granules increased again and features of the cell organelles did not display hyperfunction. These results suggest that insulin deficiency in GK rats is not caused by simple dysfunction and/or degeneration of beta-cells but rather by more complicated events within cells.
Goto-Kakizaki（GK）大鼠提供了一种2型糖尿病的遗传模型，表现出严重缺陷的胰岛素分泌，导致基础血糖升高。这种动物被广泛用于研究2型糖尿病。然而，GK大鼠胰岛的形态学特征尚未完全明确。本研究旨在利用免疫组织化学和电子显微镜技术阐明这一问题。在7、14、21和35周龄时处死GK大鼠。7周龄时未观察到胰岛结构变化。在14和21周龄时，GK大鼠出现组织病理学胰岛变化。胰岛的总体形状变得不规则，β细胞对抗胰岛素的免疫反应普遍减弱。电子显微镜显示，所谓的β颗粒数量减少，未成熟颗粒数量增加。β细胞的高尔基体发达，粗面内质网的池经常扩张，表明细胞功能亢进。然而，在35周龄时，分散到外分泌部分的β细胞的免疫反应恢复，分泌颗粒数量再次增加，细胞器特征未显示功能亢进。这些结果表明，GK大鼠的胰岛素缺乏不是由β细胞的简单功能障碍和/或退化引起的，而是由细胞内更复杂的事件引起的。
