Institute of Physiology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia.
Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia.
Exp Physiol. 2022 Nov;107(11):1326-1338. doi: 10.1113/EP090455. Epub 2022 Sep 12.
What is the central question of this study? The aim was to characterize Zucker diabetic fatty [ZDF (fa/fa)] rats and two control strains [Wistar and lean ZDF (fa/+) rats] during ageing. What is the main finding and its importance? Zucker diabetic fatty (fa/fa) rats with lower glycaemia have higher body and left ventricular weights and lower plasma gelatinase activity compared with hyperglycaemic rats. Given that type 2 diabetes is a heterogeneous metabolic disorder, the inhomogeneity of ZDF (fa/fa) rats might be beneficial in the study of its different aspects. Our experiments might promote a discussion regarding suitable normoglycaemic control animals for aged ZDF (fa/fa) rats, especially in experiments focused on myocardial tissue.
Zucker diabetic fatty [ZDF (fa/fa)] rats, which are an animal model for the study of type 2 diabetes, are considered as a uniform group in most experimental studies; however, there are indications of their increasing inhomogeneity over time. The main objective of our study was to monitor biometric and biochemical parameters of ZDF (fa/fa) rats during their development of type 2 diabetes and compare them with two control strains [Wistar and lean ZDF (fa/+) rats]. According to fasting glycaemia, ZDF (fa/fa) rats were split arbitrarily into two phenotypes: obese, ZDF (fa/fa) FAT; and diabetic, ZDF (fa/fa) DIA. Glycaemia increased progressively only in the ZDF (fa/fa) DIA animals, which also exhibited higher cholesterol levels compared with ZDF (fa/fa) FAT animals. In addition, ZDF (fa/fa) FAT rats revealed more pronounced left ventricular hypertrophy and higher body weight, differentiating them from ZDF (fa/fa) DIA rats. We also investigated the activity of matrix metalloproteinases (MMPs), which are multifunctional enzymes involved in tissue remodelling. Rats in the ZDF (fa/fa) FAT group revealed lower plasma MMP2 and MMP9 activity compared with the ZDF (fa/fa) DIA group. However, increased myocardial MMP2 activity indicated left ventricular remodelling in both ZDF phenotypes. Given that type 2 diabetes in humans is a heterogeneous metabolic disorder, the heterogeneity of ZDF (fa/fa) rats might be beneficial in the study of different aspects of this pathology. Moreover, Wistar rats could serve as a more appropriate control for aged ZDF (fa/fa) rats than the commonly used ZDF fa/+ rats, which showed an increase in left ventricular weight, carbonyl stress markers in the left myocardium and MMP2 activity in both ventricles, indicating heart remodelling processes compared with the Wistar control group.
本研究的核心问题是什么？目的是研究 Zucker 糖尿病肥胖 [ZDF（fa/fa）] 大鼠和两种对照品系 [Wistar 和 lean ZDF（fa/+）大鼠] 在衰老过程中的特征。主要发现及其重要性是什么？与高血糖大鼠相比，血糖较低的 Zucker 糖尿病肥胖（fa/fa）大鼠具有更高的体重和左心室重量以及更低的血浆明胶酶活性。鉴于 2 型糖尿病是一种代谢异质性疾病，ZDF（fa/fa）大鼠的异质性可能有益于研究其不同方面。我们的实验可能会引发关于适合老年 ZDF（fa/fa）大鼠的正常血糖对照动物的讨论，特别是在针对心肌组织的实验中。
Zucker 糖尿病肥胖（ZDF（fa/fa））大鼠是研究 2 型糖尿病的动物模型，在大多数实验研究中被视为一个均匀的群体；然而，随着时间的推移，有迹象表明它们的异质性越来越大。我们研究的主要目的是监测 ZDF（fa/fa）大鼠在 2 型糖尿病发展过程中的生物计量和生化参数，并将其与两种对照系 [Wistar 和 lean ZDF（fa/+）大鼠] 进行比较。根据空腹血糖，ZDF（fa/fa）大鼠被任意分为两种表型：肥胖型，ZDF（fa/fa）FAT；和糖尿病型，ZDF（fa/fa）DIA。只有 ZDF（fa/fa）DIA 动物的血糖水平逐渐升高，且其胆固醇水平也高于 ZDF（fa/fa）FAT 动物。此外，ZDF（fa/fa）FAT 大鼠表现出更明显的左心室肥大和更高的体重，与 ZDF（fa/fa）DIA 大鼠不同。我们还研究了基质金属蛋白酶（MMPs）的活性，MMPs 是参与组织重塑的多功能酶。与 ZDF（fa/fa）DIA 组相比，ZDF（fa/fa）FAT 组的血浆 MMP2 和 MMP9 活性较低。然而，两种 ZDF 表型的心肌 MMP2 活性增加均表明左心室重构。鉴于人类 2 型糖尿病是一种代谢异质性疾病，ZDF（fa/fa）大鼠的异质性可能有益于研究该病理学的不同方面。此外，Wistar 大鼠可能比常用的 ZDF fa/+大鼠更适合作为老年 ZDF（fa/fa）大鼠的对照，因为后者的左心室重量、左心肌羰基应激标志物和两个心室的 MMP2 活性增加，表明心脏重塑过程与 Wistar 对照组相比。
