Hirose H, Maruyama H, Kido K, Ito K, Koyama K, Tashiro Y, Saruta T
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Pancreas. 1995 Jan;10(1):71-77. doi: 10.1097/00006676-199501000-00010.
To elucidate the pathophysiology of diabetes mellitus in male WBN/Kob rats, we performed pancreatic perfusion experiments and histopathological studies. Intraperitoneal glucose tolerance tests showed a diabetic pattern in 12-month-old WBN/Kob rats. In perfused pancreata of WBN/Kob rats, both the first and the second phases of insulin secretion in response to a 16.7 mM glucose challenge were markedly reduced compared with those in age-matched Wistar rats (p < 0.01, respectively). Furthermore, the insulin secretion rate in response to glucopenia (1.4 mM) was significantly higher (p < 0.05) and the decrement in insulin secretion was significantly lower (p < 0.05) in WBN/Kob rats. The decrement in glucagon secretion with 16.7 mM glucose was significantly blunted (p < 0.001), and the glucagon secretion rate in response to glucopenia was also significantly lower in WBN/Kob rats than in controls (p < 0.01). Although insulin secretion in response to 10 mM arginine was also moderately reduced in WBN/Kob rats (p < 0.05), the glucagon secretion rates in response to 10 mM arginine were similar in the two groups. Histopathological examination revealed widespread disappearance of acinar cells and islets, inflammatory changes, and marked fibrosis in the pancreata of WBN/Kob rats. Immunohistochemical studies showed decreased numbers of B cells in the islets of WBN/Kob rats. These findings suggest that this WBN/Kob rat strain is a useful model for studying not only pathogenesis, but also pathophysiology, i.e., defective hormonal secretion, in some types of human diabetes mellitus.
为阐明雄性WBN/Kob大鼠糖尿病的病理生理学机制，我们进行了胰腺灌注实验和组织病理学研究。腹腔内葡萄糖耐量试验显示12月龄WBN/Kob大鼠呈现糖尿病模式。在WBN/Kob大鼠的灌注胰腺中，与年龄匹配的Wistar大鼠相比，对16.7 mM葡萄糖刺激的胰岛素分泌的第一相和第二相均显著降低（分别为p < 0.01）。此外，WBN/Kob大鼠对低血糖（1.4 mM）的胰岛素分泌率显著更高（p < 0.05），胰岛素分泌的减少显著更低（p < 0.05）。16.7 mM葡萄糖刺激时胰高血糖素分泌的减少显著减弱（p < 0.001），WBN/Kob大鼠对低血糖的胰高血糖素分泌率也显著低于对照组（p < 0.01）。虽然WBN/Kob大鼠对10 mM精氨酸的胰岛素分泌也适度降低（p < 0.05），但两组对10 mM精氨酸的胰高血糖素分泌率相似。组织病理学检查显示WBN/Kob大鼠胰腺中腺泡细胞和胰岛广泛消失、炎症改变和明显纤维化。免疫组织化学研究显示WBN/Kob大鼠胰岛中B细胞数量减少。这些发现表明，这种WBN/Kob大鼠品系不仅是研究某些类型人类糖尿病发病机制的有用模型，也是研究病理生理学即激素分泌缺陷的有用模型。
