Biology Department, Brandeis University, Waltham, MA, 02453, USA.
Nutrients. 2019 Jul 6;11(7):1538. doi: 10.3390/nu11071538.
The Nile rat ( is a superior model for Type-II Diabetes Mellitus (T2DM) induced by diets with a high glycemic index (GI) and glycemic load (GLoad). To better define the age and gender attributes of diabetes in early stages of progression, weanling rats were fed a high carbohydrate (hiCHO) diet for between 2 to 10 weeks. Data from four experiments compared two diabetogenic semipurified diets (Diet 133 (60:20:20, as % energy from CHO, fat, protein with a high glycemic load (GLoad) of 224 per 2000 kcal) versus Diets 73MBS or 73MB (70:10:20 with or without sucrose and higher GLoads of 259 or 295, respectively). An epidemiological technique was used to stratify the diabetes into quintiles of blood glucose (Q1 to Q5), after 2-10 weeks of dietary induction in 654 rats. The related metagenetic physiological growth and metabolic outcomes were related to the degree of diabetes based on fasting blood glucose (FBG), random blood glucose (RBG), and oral glucose tolerance test (OGTT) at 30 minutes and 60 minutes. Experiment 1 (Diet 73MBS) demonstrated that the diabetes begins aggressively in weanlings during the first 2 weeks of a hiCHO challenge, linking to diabetes susceptibility or resistance from an early age. In Experiment 2, ninety male Nile rats fed Diet 133 (60:20:20) for 10 weeks identified two quintiles of rats (Q1,Q2) that lowered their RBG between 6 weeks and 10 weeks on diet, whereas Q3-Q5 became progressively more diabetic, suggesting an ongoing struggle for control over glucose metabolism, which either stabilized or not, depending on . Experiment 3 (32 males fed 70:10:20) and Experiment 4 (30 females fed 60:20:20) lasted 8 weeks and 3 weeks respectively, for gender and time comparisons. The most telling link between a quintile rank and diabetes risk was telegraphed by energy intake (kcal/day) that established the per rat for the entire trial, which was apparent from the first week of feeding. This associated with hyperphagia across quintiles was maintained throughout the study and was mirrored in body weight gain without appreciable differences in feed efficiency. This suggests that appetite and greater growth rate linked to a fiber-free high GLoad diet were the dominant factors driving the diabetes. Male rats fed the highest GLoad diet (Diet 73MB 70:10:20, GLoad 295 per 2000 kcal for 8 weeks in Experiment 3], ate more calories and developed diabetes even more aggressively, again emphasizing the Cumulative GLoad as a primary stressor for expressing the underlying the diabetes. Thus, the Nile rat model, unlike other rodents but similar to humans, represents a superior model for high GLoad, low-fiber diets that induce diabetes from an early age in a manner similar to the dietary paradigm underlying T2DM in humans, most likely originating in childhood.
尼罗鼠(是一种用于研究高血糖指数(GI)和血糖负荷(GLoad)饮食诱导的 II 型糖尿病(T2DM)的优秀模型。为了更好地定义糖尿病在早期进展阶段的年龄和性别特征,我们用高碳水化合物(hiCHO)饮食喂养断奶大鼠 2 至 10 周。四项实验的数据比较了两种致糖尿病半纯化饮食(饮食 133(60:20:20,以能量的碳水化合物、脂肪和蛋白质的百分比表示,血糖负荷(GLoad)为 224 每 2000 千卡)与饮食 73MBS 或 73MB(70:10:20,有或没有蔗糖,血糖负荷分别为 259 或 295)。在 654 只大鼠中,用流行病学技术将糖尿病分为五个五分位数(Q1 至 Q5),这些大鼠在接受 2 至 10 周的饮食诱导后,血糖水平升高。相关的代谢生长和代谢结果与空腹血糖(FBG)、随机血糖(RBG)和口服葡萄糖耐量试验(OGTT)在 30 分钟和 60 分钟时的血糖相关,这些结果反映了糖尿病的严重程度。实验 1(饮食 73MBS)表明,糖尿病在断奶后的头 2 周内迅速在断奶大鼠中出现,这与早期的糖尿病易感性或抵抗有关。在实验 2 中,90 只雄性尼罗大鼠用饮食 133(60:20:20)喂养 10 周,确定了两群五分位数的大鼠(Q1、Q2),它们在饮食的第 6 周到第 10 周之间降低了 RBG,而 Q3-Q5 则逐渐变得更加糖尿病,这表明葡萄糖代谢的控制仍在进行中,血糖代谢的控制要么稳定,要么不稳定,这取决于。实验 3(32 只雄性大鼠,喂食 70:10:20)和实验 4(30 只雌性大鼠,喂食 60:20:20)分别持续 8 周和 3 周,以进行性别和时间比较。五分位数排名与糖尿病风险之间最明显的联系是通过能量摄入(千卡/天)来确定的,这为整个试验确定了每只大鼠的能量摄入,这从第一周的喂养就可以看出。这种与五分位数相关的摄食量增加与整个研究期间的体重增加相关,而在饲料效率方面没有明显差异。这表明,高血糖负荷、无纤维饮食所带来的食欲和更高的生长速度是推动糖尿病发生的主要因素。雄性大鼠喂食最高血糖负荷饮食(饮食 73MB70:10:20,血糖负荷为 295 每 2000 千卡,在实验 3 中持续 8 周),摄入的卡路里更多,糖尿病的发展更为严重,这再次强调了累积血糖负荷作为表达糖尿病潜在的主要应激源。因此,尼罗鼠模型与其他啮齿动物不同,但与人类相似,是一种用于研究高血糖负荷、低纤维饮食的优秀模型,这些饮食会导致糖尿病从早期开始发生,这与人类 T2DM 的饮食模式相似,很可能起源于儿童时期。