Diabetes is a chronic metabolic disease characterized by a relative or absolute lack of insulin, leading to hyperglycemia. Chronic hyperglycemia, which causes multiple complications, such as neuropathy, kidney disease, retinopathy, and increased risk of cardiovascular disease, is currently one of the most important noncommunicable diseases threatening global human health [1].
The incidence of diabetes is rising globally. According to the ninth edition of the Global Diabetes Map released by the International Diabetes Federation in 2019, 9.3% of adults currently live with diabetes, and by 2045, nearly 700 million people are predicted to be living with this disease. The prevalence of diabetes, diabetes-related deaths, and medical costs place a huge burden on the society, finance, and health care system [2]. An ideal animal model of diabetes should be established to study the pathogenesis and select the therapeutic drugs for this disease.
Many methods are currently used to establish animal models of diabetes. These models are mainly divided into models of spontaneous diabetes, such as Zucker diabetic fatty (ZDF) rats, biobreeding (BB) rats, and Goto-Kakizaki (GK) rat, and animal models of diabetes through chemical induction, such as alloxan and streptozotocin (STZ). ZDF rats were found in 1961 after Merck (M-strain) and Sherman rats were crossbred. These rats are characterized by a mutation in the leptin receptor that causes enormous appetite, and the rats become obese by 4 weeks of age. These rats also have hyperinsulinemia, hyperlipidemia, hypertension, and impaired glucose tolerance [3]. BB rats are derived from a distant relative, the Wistar rat. After puberty, the BB rats develop diabetes, with rates similar between males and females, and 90% of the rats develop this disease between 8 weeks and 16 weeks of age. The diabetes phenotype is quite severe and characterized by the development of hyperglycemia, weight loss from hypoinsulinemia, and ketouria, which requires insulin therapy to survive [4]. GK rats develop mild hyperglycemia early in life and are considered as a nonobese model, and all adult GK rats of both sexes show type 2 diabetes [5]. Alloxan and STZ are considered the most effective diabetes-promoting drugs used in diabetes research and are cytotoxic glucose analogs [6]. Although their cytotoxicity is achieved by different pathways, their selective actions on the β cells are the same; that is, both drugs cause insulin deficiency. The STZ pathway is targeted β‑cell apoptosis with chemical that induces DNA alkylation, while alloxan is targeted β‑cell destruction with chemical that induces oxidative stress [7–9]. Compared with alloxan, STZ is more stable and the best choice for repeatedly inducing diabetes in the experimental animals [10]. However, the physicochemical properties and related toxicity of STZ remain major obstacles for researchers who use STZ to treat diabetes in animals.
Another major challenge for STZ-induced diabetes models is how to maintain the suitability, repeatability, and inductivity of diabetes with minimal animal mortality. The lack of appropriate use of STZ has been associated with increased mortality and animal suffering [11]. Therefore, several factors, such as the preparation method, stability, appropriate dose, diet plan, animal species (related to age, weight, and gender), and target blood glucose level representing hyperglycemia should be considered when STZ is used in animals.
In this study, the effects of the gender of Sprague-Dawley (SD) rats, dose of STZ injection, and dietary conditions on the body weight, blood glucose, modeling rate, and mortality were compared.