de Campos Kleber Eduardo, Sinzato Yuri Karen, Pimenta Walkyria de Paula, Rudge Marilza Vieira Cunha, Damasceno Débora Cristina
Laboratory of Experimental Research of Gynecology and Obstetrics, Department of Gynecology and Obstetrics, School of Medicine of Botucatu--São Paulo State University (Unesp)--São Paulo State, CEP 18618-000, Brazil.
Life Sci. 2007 Oct 27;81(19-20):1473-8. doi: 10.1016/j.lfs.2007.09.016. Epub 2007 Oct 2.
This study aimed to evaluate whether maternal obesity leads to the onset of diabetes in adult Wistar rats offspring. MSG solution neonatally administration induced obesity in rats (F(1)MSG group, n=30); and saline solution was also administrated to control rats (F(1)CON group, n=13). In 3rd month of age, both control and MSG groups were mated for offspring (generation F(2)), named as F(2)CON, n=28 and F(2)MSG groups, n=15; and so both generations were studied until 7th month of life. Lee Index was measured for experimental obesity validation from 5th to 7th month. Glycemia was weekly determined during pregnancy and monthly from 3rd to 7th month. In the end of experimental period all rats were submitted to oral glucose tolerance test (OGTT), with estimation of total area under the curve (AUC); and insulin tolerance test (ITT). Rats were then anesthetized and killed. Data were statistically analyzed with significance level of p<0.05. Lee Index has confirmed obesity in all MSG rats. Glycemic levels comparisons between generations showed significant maternal interference in control and MSG groups. OGTT analysis showed higher glycemia in obese rats (F(1)MSG) and their offspring (F(2)MSG) as compared to their respective controls; and MSG groups increased AUC from OGTT. As regards ITT, F(2)MSG showed higher glycemia at 30 and 120 min, suggesting a delay of insulin action decreasing. Although glucose intolerance and insulin resistance clinical conditions represent as a factors for type 2 Diabetes mellitus development, this experimental model proposal was not efficient to induce type 2 Diabetes mellitus, but for obesity developing, glucose intolerance and insulin resistance in successive generations of rats.
本研究旨在评估母体肥胖是否会导致成年Wistar大鼠后代患糖尿病。新生期给予味精溶液可诱导大鼠肥胖（F(1)味精组，n = 30）；同时也给对照大鼠给予盐溶液（F(1)对照组，n = 13）。在3月龄时，将对照组和味精组的大鼠进行交配以产生后代（F(2)代），分别命名为F(2)对照组，n = 28和F(2)味精组，n = 15；对这两代大鼠进行研究直至7月龄。从第5个月到第7个月测量李氏指数以验证实验性肥胖。在怀孕期间每周测定血糖，从第3个月到第7个月每月测定一次。在实验期结束时，所有大鼠均接受口服葡萄糖耐量试验（OGTT），并估算曲线下总面积（AUC）；以及胰岛素耐量试验（ITT）。然后将大鼠麻醉并处死。数据采用p<0.05的显著性水平进行统计学分析。李氏指数证实所有味精大鼠均肥胖。两代之间血糖水平的比较显示对照组和味精组存在显著的母体干扰。OGTT分析显示，与各自的对照组相比，肥胖大鼠（F(1)味精组）及其后代（F(2)味精组）的血糖更高；味精组OGTT的AUC增加。关于ITT，F(2)味精组在30分钟和120分钟时血糖更高，表明胰岛素作用延迟减弱。尽管葡萄糖不耐受和胰岛素抵抗的临床状况是2型糖尿病发展的因素，但该实验模型方案未能有效诱导2型糖尿病，而是导致了大鼠连续几代出现肥胖、葡萄糖不耐受和胰岛素抵抗。
