Division of Laboratory Animal Science, Nippon Medical School, Tokyo, Japan.
Exp Anim. 2010;59(5):623-30. doi: 10.1538/expanim.59.623.
Original WBN/Kob male rats commonly develop chronic pancreatitis by the age of 3 months, while diabetes mellitus occurs at 9 months. In contrast, female rats of this strain do not show pancreatitis or diabetes. The WBN/Kob-fatty rat is a homozygous (fa/fa) congenic strain for the fa allele of the leptin receptor gene (Lepr). In WBN/Kob-fatty rats, both females and males provide a model of non-insulin-dependent diabetes with obesity. The leptin receptor fatty gene (Lepr(fa)) induces obesity and hyperphagia. In the present study, we examined the effect of dietary restriction on pancreatitis and diabetes in female WBN/Kob-fatty rats. Five female fatty rats comprised a restricted feeding group with paired-feeding from 3 to 13 weeks of age, and five female lean rats comprised a control group with paired-feeding. At 13 weeks of age, two of the five female fatty rats of the control group developed diabetes mellitus, while no female fatty rats of the restricted feeding group developed diabetes mellitus. At this stage, pathological changes of the pancreas were observed in female fatty rats. All female fatty rats showed severe interlobular, intra-lobular and intra-islet fibrosis. In female fatty rats of the restricted feeding group, pathological changes of the pancreas were milder those of the free-feeding fatty group. Although dietary restriction could not completely prevent pancreatitis in female fatty rats, the development of diabetes was inhibited by its reduction of the severity of pancreatitis.
WBN/Kob 雄性大鼠通常在 3 个月大时就会发展为慢性胰腺炎，而糖尿病则在 9 个月大时发生。相比之下，该品系的雌性大鼠既不会发生胰腺炎，也不会发生糖尿病。WBN/Kob 肥胖大鼠是瘦素受体基因（Lepr）fa 等位基因的纯合子（fa/fa）同源系。在 WBN/Kob 肥胖大鼠中，雌性和雄性均提供了肥胖伴非胰岛素依赖性糖尿病的模型。瘦素受体肥胖基因（Lepr(fa)) 可导致肥胖和多食。在本研究中，我们研究了饮食限制对雌性 WBN/Kob 肥胖大鼠胰腺炎和糖尿病的影响。5 只雌性肥胖大鼠组成了限制喂食组，从 3 周到 13 周龄进行配对喂食，5 只雌性 lean 大鼠组成了对照组，进行配对喂食。在 13 周龄时，对照组的 5 只雌性肥胖大鼠中有 2 只发生了糖尿病，而限制喂食组的雌性肥胖大鼠无一例发生糖尿病。在这个阶段，观察到了雌性肥胖大鼠胰腺的病理变化。所有雌性肥胖大鼠均表现出严重的小叶间、小叶内和胰岛内纤维化。在限制喂食组的雌性肥胖大鼠中，胰腺的病理变化较自由喂食肥胖组更为轻微。尽管饮食限制不能完全预防雌性肥胖大鼠的胰腺炎，但它通过减轻胰腺炎的严重程度，抑制了糖尿病的发生。
