Paniagua-Sancho María, Casanova Alfredo G, Rodríguez-Estévez Lucía, Cruz-González Ignacio, López-Hernández Francisco J, Martínez-Salgado Carlos
Translational Research On Renal and Cardiovascular Diseases (TRECARD), Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain; Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain.
Cardiology Department, University Hospital of Salamanca, 37007 Salamanca, Spain.
Methods. 2025 Feb;234:223-232. doi: 10.1016/j.ymeth.2025.01.002. Epub 2025 Jan 4.
The high prevalence of type 2 diabetes and atherosclerosis makes essential the availability of in vivo experimental models that accurately replicate the pathophysiological mechanisms of these diseases. Apolipoprotein E knockout mice (ApoE) have been used in atherosclerosis studies, and the db/db mice show hyperphagia and obesity. Mice harbouring both alterations (i.e., ApoE) are expected to develop combined features of type 2 diabetes, obesity and accelerated atherosclerosis. To deepen into their pathophysiological profile and further assess their potential as an experimental model, we studied their mortality and their pancreatic, cardiac, and renal phenotype. We analysed during 6 months the glycemic and lipid profile, pancreatic, cardiac and renal structure and function and atherosclerosis in ApoE mice. ApoE mice show increases in plasma glucose (although without statistical significance) and glucagon levels, total cholesterol, triglycerides and HDL-cholesterol and in both insulin-producing β and glucagon producing α cells, and in the tissue expression of both hormones with respect to control (C57BL/6) mice; they show a remarkably high degree of atherosclerosis, higher left ventricular ejection fraction. Although renal function is normal, glucose, sodium and albumin excretion and urinary flow are increased with respect to control mice. Summarizing, ApoE mice constitute a suitable experimental model for the study of type 2 diabetes associated with atherosclerosis.
2型糖尿病和动脉粥样硬化的高患病率使得准确复制这些疾病病理生理机制的体内实验模型变得至关重要。载脂蛋白E基因敲除小鼠（ApoE）已用于动脉粥样硬化研究，而db/db小鼠表现出食欲亢进和肥胖。同时具有这两种改变（即ApoE）的小鼠预计会出现2型糖尿病、肥胖和加速动脉粥样硬化的综合特征。为了深入了解它们的病理生理特征并进一步评估它们作为实验模型的潜力，我们研究了它们的死亡率以及胰腺、心脏和肾脏表型。我们在6个月内分析了ApoE小鼠的血糖和血脂谱、胰腺、心脏和肾脏结构与功能以及动脉粥样硬化情况。ApoE小鼠的血糖（尽管无统计学意义）和胰高血糖素水平、总胆固醇、甘油三酯和高密度脂蛋白胆固醇升高，胰岛素分泌β细胞和胰高血糖素分泌α细胞以及这两种激素的组织表达相对于对照（C57BL/6）小鼠均增加；它们表现出高度显著的动脉粥样硬化，左心室射血分数更高。尽管肾功能正常，但相对于对照小鼠，葡萄糖、钠和白蛋白排泄以及尿流量增加。总之，ApoE小鼠构成了研究与动脉粥样硬化相关的2型糖尿病的合适实验模型。
