Central Pharmaceutical Research Institute, Japan Tobacco Inc, Takatsuki, Osaka, Japan.
Exp Anim. 2010;59(1):73-84. doi: 10.1538/expanim.59.73.
Obesity, hyperglycemia, hyperlipidemia, and diabetes-associated complications appear at younger ages (6-8 weeks) in the male Spontaneously Diabetic Torii-Lepr(fa) (SDT-fa/fa) rat than in the male original SDT (SDT-+/+) rat. However, the incidence and progression of diabetes mellitus and diabetic complications in the female SDT-fa/fa rat have not been reported in detail. In the present study, the pathophysiological features of the female SDT-fa/fa rat were examined, and compared with those of the female SDT-+/+ rat. Female SDT-fa/fa rats showed hyperphagia, obesity, hyperglycemia, and hyperlipidemia from 5 or 6 weeks of age, and hyperinsulinemia was observed from 5 to 12 weeks. Pathological changes pancreatic islets were observed from 8 weeks. Renal function parameters, such as urine volume and urinary protein, increased from 16 weeks, and pathological findings in the renal tubule, and cataracts were also observed from 16 weeks. Increases of visceral and subcutaneous fats were obvious during the observation period. In pair-feeding with SDT-+/+ rats, SDT-fa/fa rats showed improved hyperglycemia and hypertriglycemia, but hypercholesterolemia was not entirely improved during the study period. Female SDT-fa/fa rats showed diabetes mellitus and diabetes-associated complications at young ages, and fat accumulation was remarkable. Suppression of hyperphagia in SDT-fa/fa rats was effective at improving hyperglycemia and hypertriglycemia. In conclusion, the female SDT-fa/fa rat has the potential to become an important animal model of type 2 diabetes mellitus with obesity, especially for women, for which few models currently exist.
肥胖症、高血糖、高血脂和糖尿病相关并发症在雄性自发性糖尿病 Torii-Lepr(fa)(SDT-fa/fa)大鼠中比在雄性原始 SDT(SDT-+/+)大鼠中更早出现(6-8 周龄)。然而,雌性 SDT-fa/fa 大鼠的糖尿病及其并发症的发生率和进展尚未详细报道。在本研究中,我们检查了雌性 SDT-fa/fa 大鼠的病理生理学特征,并与雌性 SDT-+/+大鼠进行了比较。雌性 SDT-fa/fa 大鼠从 5 或 6 周龄开始出现贪食、肥胖、高血糖和高血脂,并且从 5 周到 12 周观察到高胰岛素血症。从 8 周开始观察到胰腺胰岛的病理变化。肾功能参数,如尿量和尿蛋白,从 16 周开始增加,并且从 16 周开始还观察到肾小管的病理发现和白内障。在观察期间,内脏和皮下脂肪增加明显。在与 SDT-+/+大鼠进行配对喂养时,SDT-fa/fa 大鼠的高血糖和高三酰甘油血症得到改善,但在研究期间高胆固醇血症并未完全改善。雌性 SDT-fa/fa 大鼠在年轻时出现糖尿病和糖尿病相关并发症,并且脂肪堆积明显。抑制 SDT-fa/fa 大鼠的贪食症对改善高血糖和高三酰甘油血症有效。总之,雌性 SDT-fa/fa 大鼠具有成为肥胖症 2 型糖尿病重要动物模型的潜力,特别是对于目前很少有模型的女性。