Foster Biomedical Research Laboratory, Brandeis University, Waltham, MA, USA, 02454.
Nutr Metab (Lond). 2010 Apr 15;7:29. doi: 10.1186/1743-7075-7-29.
The prevalence of Metabolic Syndrome and related chronic diseases, among them non-insulin-dependent (type 2) diabetes mellitus, are on the rise in the United States and throughout the world. Animal models that respond to environmental stressors, such as diet, are useful for investigating the outcome and development of these related diseases.
Within this context, growth and energy relationships were characterized in the Nile rat, an exotic African rodent, as a potential animal model for diet-induced type 2 diabetes mellitus and Metabolic Syndrome.
Compiled data from several studies established the relationship between age, body weight gain (including abdominal adiposity), food and water consumption, and blood glucose levels as determinants of diabetes in male and female Nile rats. Glucose Tolerance Testing, insulin, HbA1c, blood pressure measurements and plasma lipids further characterized the diabetes in relation to criteria of the Metabolic Syndrome, while diet modification with high-fat, low-fiber or food restriction attempted to modulate the disease.
The Nile rat fed lab chow demonstrates signs of the Metabolic Syndrome that evolve into diet-induced non-insulin-dependent (type 2) diabetes mellitus characterized by hyperinsulinemia with rising blood glucose (insulin resistance), abdominal adiposity, and impaired glucose clearance that precedes increased food and water intake, as well as elevated HbA1c, marked elevation in plasma triglycerides and cholesterol, microalbuminuria, and hypertension. Males are more prone than females with rapid progression to diabetes depending on the challenge diet. In males diabetes segregated into early-onset and late-onset groups, the former related to more rapid growth and greater growth efficiency for the calories consumed. Interestingly, no correlation was found between blood glucose and body mass index (overall adiposity) in older male Nile rats in long term studies, whereas blood glucose and the perirenal fat pad, as well as liver and kidney weight, were positively related to early-onset diabetes. Rats weaned early (4-5 wks) and challenged with a high-fat Western-type diet developed diabetes faster, and body fat accumulation was more apparent, whereas food restriction curtailed it.
The Nile rat fed typical rodent diets develops hyperinsulinemia that precedes hyperglycemia (insulin resistance) leading to diet-induced type 2 diabetes associated with hypertriglyceridemia, hypercholesterolemia, and hypertension. Dietary modulation affected growth rate (weight gain and central adiposity) to impact disease progression. This rodent model represents a novel system of gene-diet interactions affecting energy utilization that can provide insight into the prevention and treatment of the type 2 diabetes and Metabolic Syndrome.
在美国和世界各地，代谢综合征及相关慢性疾病（包括非胰岛素依赖型（2 型）糖尿病）的患病率呈上升趋势。对于像饮食这样的环境应激源有反应的动物模型，可用于研究这些相关疾病的结果和发展。
在这种情况下，我们以一种外来的非洲啮齿动物——尼罗鼠为模型，研究了生长和能量关系，作为饮食诱导 2 型糖尿病和代谢综合征的潜在动物模型。
综合多项研究的数据，确定了年龄、体重增长（包括腹部肥胖）、食物和水的消耗以及血糖水平之间的关系，作为雄性和雌性尼罗鼠患糖尿病的决定因素。葡萄糖耐量试验、胰岛素、HbA1c、血压测量和血浆脂质进一步将糖尿病与代谢综合征的标准相关联，而高脂肪、低纤维或饮食限制等饮食改变则试图调节疾病。
用实验室饲料喂养的尼罗鼠表现出代谢综合征的迹象，这些迹象发展为饮食诱导的非胰岛素依赖型（2 型）糖尿病，其特征是随着血糖升高（胰岛素抵抗）而出现高胰岛素血症、腹部肥胖和葡萄糖清除受损，这先于食物和水摄入增加以及 HbA1c 升高、血浆甘油三酯和胆固醇显著升高、微量白蛋白尿和高血压。雄性比雌性更容易患上糖尿病，而且取决于所面临的饮食挑战，糖尿病的进展速度也更快。在雄性中，糖尿病分为早发和晚发两组，前者与卡路里摄入的更快增长和更高的生长效率有关。有趣的是，在长期研究中，老年雄性尼罗鼠的血糖与体重指数（整体肥胖）之间没有相关性，而血糖与肾周脂肪垫以及肝、肾重量呈正相关，与早发糖尿病有关。在 4-5 周龄时早期断奶并接受高脂肪西式饮食的大鼠更快地发展为糖尿病，并且脂肪积累更为明显，而饮食限制则减缓了糖尿病的发展。
用典型的啮齿动物饲料喂养的尼罗鼠会出现胰岛素血症，这先于高血糖（胰岛素抵抗），导致饮食诱导的 2 型糖尿病与高甘油三酯血症、高胆固醇血症和高血压有关。饮食调节会影响生长速度（体重增加和中心性肥胖），从而影响疾病的进展。这种啮齿动物模型代表了一种新的基因-饮食相互作用系统，影响能量利用，可以深入了解 2 型糖尿病和代谢综合征的预防和治疗。
