Departments of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Division of Biomedical Sciences, Faculty of Medicine, Memorial University, St. John's, Newfoundland, Canada.
Exp Physiol. 2022 Apr;107(4):265-282. doi: 10.1113/EP089947. Epub 2022 Mar 8.
What is the topic of this review? The Zucker Diabetic-Sprague Dawley (ZDSD) rat is in the early adoption phase of use by researchers in the fields of diabetes, including prediabetes, obesity and metabolic syndrome. It is essential that physiology researchers choose preclinical models that model human type 2 diabetes appropriately and are aware of the limitations on experimental design. What advances does it highlight? Our review of the scientific literature finds that although sex, age and diets contribute to variability, the ZDSD phenotype and disease progression model the characteristics of humans who have prediabetes and diabetes, including co-morbidities.
Type 2 diabetes (T2D) is a prevalent disease and a significant concern for global population health. For persons with T2D, clinical treatments target not only the characteristics of hyperglycaemia and insulin resistance, but also co-morbidities, such as obesity, cardiovascular and renal disease, neuropathies and skeletal bone conditions. The Zucker Diabetic-Sprague Dawley (ZDSD) rat is a rodent model developed for experimental studies of T2D. We reviewed the scientific literature to highlight the characteristics of T2D development and the associated phenotypes, such as metabolic syndrome, cardiovascular complications and bone and skeletal pathologies in ZDSD rats. We found that ZDSD phenotype characteristics are independent of leptin receptor signalling. The ZDSD rat develops prediabetes, then progresses to overt diabetes that is accelerated by introduction of a timed high-fat diet. In male ZDSD rats, glycated haemoglobin (HbA1c) increases at a constant rate from 7 to >30 weeks of age. Diabetic ZDSD rats are moderately hypertensive compared with other rat strains. Diabetes in ZDSD rats leads to endothelial dysfunction in specific vasculatures, impaired wound healing, decreased systolic and diastolic cardiac function, neuropathy and nephropathy. Changes to bone composition and the skeleton increase the risk of bone fractures. Zucker Diabetic-Sprague Dawley rats have not yet achieved widespread use by researchers. We highlight sex-related differences in the ZDSD phenotype and gaps in knowledge for future studies. Overall, scientific data support the premise that the phenotype and disease progression in ZDSD rats models the characteristics in humans. We conclude that ZDSD rats are an advantageous model to advance understanding and discovery of treatments for T2D through preclinical research.
这篇综述的主题是什么？Zucker 糖尿病-斯普拉格·道利（ZDSD）大鼠正处于被糖尿病领域研究人员（包括糖尿病前期、肥胖和代谢综合征）采用的早期阶段。生理学家选择适当模拟人类 2 型糖尿病的临床前模型并了解实验设计的局限性至关重要。它突出了哪些进展？我们对科学文献的综述发现，尽管性别、年龄和饮食会导致变异性，但 ZDSD 表型和疾病进展模型模拟了患有糖尿病前期和糖尿病的人类的特征，包括合并症。
2 型糖尿病（T2D）是一种常见疾病，也是全球人口健康的重大关注点。对于 T2D 患者，临床治疗不仅针对高血糖和胰岛素抵抗的特征，还针对肥胖、心血管和肾脏疾病、神经病变和骨骼疾病等合并症。Zucker 糖尿病-斯普拉格·道利（ZDSD）大鼠是一种为 T2D 的实验研究开发的啮齿动物模型。我们综述了科学文献，以突出 ZDSD 大鼠 T2D 发展的特征及其相关表型，如代谢综合征、心血管并发症以及骨骼和骨骼病理学。我们发现，ZDSD 表型特征与瘦素受体信号无关。ZDSD 大鼠会发展为糖尿病前期，然后进展为显性糖尿病，通过引入定时高脂肪饮食会加速这一过程。在雄性 ZDSD 大鼠中，糖化血红蛋白（HbA1c）从 7 周到 30 周以上的年龄以恒定速度增加。与其他大鼠品系相比，糖尿病 ZDSD 大鼠有中度高血压。ZDSD 大鼠的糖尿病会导致特定血管的内皮功能障碍、伤口愈合受损、收缩和舒张心脏功能下降、神经病变和肾病。骨骼成分和骨骼的变化会增加骨折的风险。Zucker 糖尿病-斯普拉格·道利（ZDSD）大鼠尚未被研究人员广泛采用。我们强调了 ZDSD 表型的性别相关差异以及未来研究中的知识空白。总的来说，科学数据支持 ZDSD 大鼠的表型和疾病进展模型模拟人类特征的前提。我们得出结论，ZDSD 大鼠是通过临床前研究推进对 2 型糖尿病治疗的理解和发现的有利模型。
