Okauchi N, Mizuno A, Zhu M, Ishida K, Sano T, Noma Y, Shima K
Department of Laboratory Medicine, School of Medicine, University of Tokushima, Japan.
Diabetes Res Clin Pract. 1995 Jul;29(1):1-10. doi: 10.1016/0168-8227(95)01114-s.
We studied whether obesity or inheritance was the more important factor in the development of non-insulin-dependent diabetes mellitus (NIDDM) using female Otsuka-Long-Evans-Tokushima Fatty rats (OLETF) possessing one of the diabetic genes, ODB-1, and male Long-Evans-Tokushima-Otsuka rats (LETO) possessing no ODB-1, neither of which were diabetic when bred normally. Diabetes-resistant male LETO rats and female OLETF rats (4 weeks old) were assigned to three groups of 6 rats each, respectively; two groups in which obesity was induced by high calorie 'cafeteria' diet (D), or ventromedial hypothalamus lesions (V) with normal chow diet and a control group fed on normal chow (C). Six male OLETF rats were used as NIDDM positive controls. The mean daily energy intakes of obese male LETO and female OLETF rats were higher than those of the respective C groups. At 27 weeks of age, the average body weights of the obese LETO and female OLETF rats were significantly higher than those of the respective C groups and similar to that of the male OLETF group. Abdominal fat deposits of the obese groups were significantly higher than those of the respective C groups. At 28 weeks of age, the cumulative incidence of diabetes mellitus in obese LETO rats was 0% in group D and 17% in group V, while that of obese female OLETF rats in groups D and V were 100%. At 29 weeks of age, the plasma immunoreactive insulin (IRI) responses to glucose in obese female OLETF rats, groups D and V, were higher than that in group C. In obese LETO rats, insulin-stimulated glucose disposal in vivo was similar to that in group C, but in obese female OLETF rats, it was reduced to 41% in group D and 37% in group V of that in group C. Sections of islets of the pancreas of obese LETO rats appeared histologically normal, whereas those of obese female OLETF rats showed enlarged multilobulated fibrotic islets. These results demonstrate that obesity is necessary, but not sufficient alone for the development of NIDDM in these rat models.
我们使用携带糖尿病基因ODB-1之一的雌性大冢-长-埃文斯-德岛肥胖大鼠（OLETF）和不携带ODB-1的雄性长-埃文斯-德岛-大冢大鼠（LETO），研究肥胖或遗传因素在非胰岛素依赖型糖尿病（NIDDM）发生发展中哪个更为重要，这两种大鼠在正常繁殖时均不患糖尿病。将抗糖尿病的雄性LETO大鼠和雌性OLETF大鼠（4周龄）分别分为每组6只大鼠的三组；两组通过高热量“自助式”饮食（D组）或腹内侧下丘脑损伤（V组）诱导肥胖，同时给予正常饲料，还有一组为给予正常饲料的对照组（C组）。6只雄性OLETF大鼠用作NIDDM阳性对照。肥胖的雄性LETO大鼠和雌性OLETF大鼠的平均每日能量摄入量高于各自的C组。在27周龄时，肥胖的LETO大鼠和雌性OLETF大鼠的平均体重显著高于各自的C组，且与雄性OLETF组相似。肥胖组的腹部脂肪沉积显著高于各自的C组。在28周龄时，肥胖的LETO大鼠在D组糖尿病累积发病率为0%，在V组为17%，而肥胖的雌性OLETF大鼠在D组和V组的糖尿病累积发病率均为100%。在29周龄时，肥胖的雌性OLETF大鼠D组和V组对葡萄糖的血浆免疫反应性胰岛素（IRI）反应高于C组。在肥胖的LETO大鼠中，胰岛素刺激的体内葡萄糖处置与C组相似，但在肥胖的雌性OLETF大鼠中，D组降至C组的41%，V组降至37%。肥胖的LETO大鼠胰腺胰岛切片在组织学上看起来正常，而肥胖的雌性OLETF大鼠的胰岛切片显示胰岛肿大、多叶且纤维化。这些结果表明，在这些大鼠模型中，肥胖是NIDDM发生发展所必需的，但单独肥胖并不足以导致NIDDM。
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