Ishida K, Mizuno A, Sano T, Noma Y, Shima K
Department of Laboratory Medicine, School of Medicine, University of Tokushima, Japan.
Horm Metab Res. 1995 Sep;27(9):398-402. doi: 10.1055/s-2007-979987.
Morphological changes of the pancreas and impairment of pancreatic B-cell function in a model rat (Otsuka Long Evans Tokushima Fatty [OLETF]) with non-insulin dependent diabetes mellitus might be the result of over-activity of B-cells to compensate for insulin insensitivity. To test this possibility, we studied whether the histological and functional alterations in the pancreas of male OLETF rats were improved by treatment with insulin for a certain period, which might reduce the burden to B-cells. Groups of 6 male OLETF rats and 5 or 4 male non-diabetic control Long Evans Tokushima Otsuka (LETO) rats received injections of insulin (Ultralente MC; 10 U/kg/day to OLETF rats, 5 U/kg/day to LETO rats) or saline subcutaneously, once a day for 3 weeks from 24 weeks of age. Then their insulin responses to glucose (200 mg/dl) and arginine (10 mmol/l) were examined by perfusion of the pancreas. The morphological features of their pancreata were also examined. The insulin response to glucose in OLETF rats treated with insulin was significantly higher than that of OLETF rats treated with saline (sigma IRI 142.5 +/- 27.0 vs. 37.4 +/- 6.3 ng/ml.20 min, p < 0.05) and unlike in the latter showed the normal two phases. The morphological changes of the pancreas in the insulin-treated OLETF rats were remarkably ameliorated, animals showing no enlargement and only slight fibrosis of islets. Thus treatment with insulin was effective for preventing B-cell dysfunction and morphological changes of the pancreas in NIDDM model rats.
非胰岛素依赖型糖尿病模型大鼠（大冢长- Evans 德岛肥胖[OLETF]）胰腺的形态学变化及胰岛β细胞功能受损可能是β细胞过度活跃以代偿胰岛素不敏感的结果。为验证这一可能性，我们研究了给予雄性OLETF大鼠一定时期的胰岛素治疗是否能改善胰腺的组织学和功能改变，这可能会减轻β细胞的负担。将6只雄性OLETF大鼠和5只或4只雄性非糖尿病对照长- Evans 德岛大冢（LETO）大鼠分为几组，从24周龄开始，每天皮下注射胰岛素（超长效MC；OLETF大鼠10 U/kg/天，LETO大鼠5 U/kg/天）或生理盐水，持续3周。然后通过胰腺灌注检查它们对葡萄糖（200 mg/dl）和精氨酸（10 mmol/l）的胰岛素反应。还检查了它们胰腺的形态特征。胰岛素治疗的OLETF大鼠对葡萄糖的胰岛素反应明显高于生理盐水治疗的OLETF大鼠（胰岛素释放指数142.5±27.0 vs. 37.4±6.3 ng/ml·20分钟，p<0.05），且与后者不同，呈现正常的两个阶段。胰岛素治疗的OLETF大鼠胰腺的形态学变化明显改善，动物的胰岛无肿大，仅有轻微纤维化。因此，胰岛素治疗对预防非胰岛素依赖型糖尿病模型大鼠的β细胞功能障碍和胰腺形态学变化有效。
