Zucker Diabetic Fatty Rats for Research in Diabetes

Abstract

The rising incidence of diabetes mellitus (DM) worldwide presents a global public health problem. DM is classified into two main groups: type 1 (T1DM) and type 2 (T2DM). T1DM requires insulin treatment. T2DM is complex, heterogeneous, polygenic disease defined primarily by insulin resistance, ongoing hyperglycemia, and β cells' dysfunction. For research in diabetes, an appropriate experimental model reflecting symptoms and complications of human T2DM is required for understanding the pathogenesis, molecular nature, and the possibilities of the treatment. Among the many animal models, rodent models that develop DM spontaneously are frequently used in the studies due to their similarity to the humans and economic effectiveness. This work gives a detailed overview of the literature, covering the characteristic of DM, its symptoms and complications, the description of Zucker diabetic fatty (ZDF) rats as an appropriate model for research in T2DM, and the possibility of the treatment.spontaneously diabetic Tori (SDT) rats, Kuo Kondo (KK) mice, ob/ob+/+ mice, and db/db+/+ mice [84]. GK rats are nonobese Wistar substrain which develops T2DM early [86]. Male OLETS rats suffer from diabetes at 18-25 weeks of age. The symptoms include polyphagia, mild obesity, hypertriglyceridemia, hyperinsulinemia, and impaired glucose tolerance in 16 weeks of age [87]. Tori SDT rat is inbred strain of Sprague-Dawley rat. Male individuals have high glucose levels by 20 weeks, pancreatic islet histopathology, hemorrhage in pancreatic islets, and inflammatory cell infiltration with fibroblasts, prior to diabetes glucose intolerance with hypoinsulinemia [88].KK mice are a polygenic model of obesity and T2DM. They are characterized by insulin resistance, hyperinsulinemia, and hyperphagia [89]. The ob/ob+/+ mice carry a mutation in the leptin gene, manifested as obesity, hyperglycemia, impaired glucose intolerance, and hyperinsulinemia [90]. The db/db+/+ mice have a leptin receptor mutation, are spontaneously hyperphagic, and suffer from obesity, hyperglycemia, hyperinsulinemia, and insulin resistance within the first month of life [91]. The advantages of ZDF rats in diabetes research are mainly due to the fact that it is a spontaneous model for T2DM research. It shows characteristics such as hyperglycemia, obesity, hyperphagia, polyuria, insulin disorders, and dyslipidemia due to the mutation in the leptin receptor gene and provides an appropriate model for common human T2DM. Moreover, these rats are calm and dispassionate; the handling and manipulation with them is comfortable.

Tenovin-1 Ameliorates Renal Fibrosis in High-Fat-Diet-Induced Diabetic Nephropathy via Antioxidant and Anti-Inflammatory Pathways

“…ZDF rats have hyperglycemia and dyslipidemia from an early age (2 months), which worsens as they age (8 month of age). ZDF rats’ renal histology at 8 months revealed pathological alterations, including glomerular sclerosis with thickening of the Bowman capsule and retraction of the tuft, tubular atrophy and dilatation, and hyaline casts [ 27 , 28 ]. The ZDF rats were fed a high-fat diet in order to make the nephropathy more severe and shorten the study’s duration.…”

Animal models for type 1 and type 2 diabetes: advantages and limitations

“…One significant limitation is that these animals exhibit only mild glucose intolerance which makes their utility as a T2D model questionable, given that human T2D typically involves more severe glucose intolerance ( 128 ). Furthermore, while the lipid profile is altered in these rats, they show an increase in very low-density lipoproteins (VLDL) and high-density lipoproteins (HDL), but not in low-density lipoprotein (LDL) cholesterol ( 127 , 128 ). Therefore, they are not suitable models for atherogenesis studies.…”

“…It is largely utilized as a model of human obesity accompanied with hyperlipidemia and hypertension ( 24 , 26 ). The Zucker fatty rat model offers specific advantages for type 2 diabetes (T2D) research primarily due to its spontaneous nature, closely mimicking common human T2DM characteristics such as hyperglycemia, obesity, hyperphagia, polyuria, insulin disorders, and dyslipidemia ( 127 ). Additionally, these rats are also noted for being calm and easy to handle, which facilitates their use in various experimental settings ( 127 , 128 ).…”

“…Therefore, they are not suitable models for atherogenesis studies. Additionally, despite having high systolic blood pressure values after 28 weeks, they are not considered a model for hypertension, which can be a significant comorbidity in human T2D ( 127 , 128 ). It is worth noting that selective inbreeding of fa/fa rat for hyperglycemia resulted in the development of the ZDF rat model, which develops more severe diabetes than the Zucker fatty rats but only in male mice, thus reducing some of these limitations ( 24 , 93 ).…”

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“…According to Capcarova and Kalafova, 6 the rising incidence of diabetes mellitus (DM) worldwide presents a global public health problem. The use of medicinal plants and their derived bioactive compounds to cure various ailments, including metabolic disorders, has been a preference since the earliest of times.…”