Diabetes is one of the five leading causes of death in the world, with type 2 diabetes occurring more frequently than type 1. Management of diabetes without side effects is still a challenge and therefore new strategies need to be examined. Because of difficulties in human research, animal models of diabetes are useful research tools for this purpose and rodent models of type 2 diabetes are the first choice. The aim of this study is an overview on one of the most frequently used models of type 2 diabetes in rat, induced by streptozotocin and nicotinamide, considering its advantages and disadvantages for diabetes research in humans.
Streptozotocin (STZ) is the most used diabetogenic chemical for creating rat models of type 1 and type 2 diabetes. Despite ~60 years of using STZ in animal diabetes research, some prevailing views about STZ preparation and use are not supported by evidence. Here, we provide practical guides for using STZ to induce diabetes in rats. Susceptibility to the diabetogenic effect of STZ is inversely related to age, and males are more susceptible to STZ than females. Wistar and Sprague-Dawley rats, the most commonly-used rat strains, are sensitive to STZ, but some strains (e.g., Wistar-Kyoto rats) are less sensitive. STZ is mostly injected intravenously or intraperitoneally, but its intravenous injection produces more stable hyperglycemia. Despite the prevailing view, no fasting is necessary before STZ injection, and injection of its anomer-equilibrated solutions (i.e., more than 2 hours of dissolving) is recommended. Mortality following the injection of diabetogenic doses of STZ is due to severe hypoglycemia (during the first 24 h) or severe hyperglycemia (24 h after the injection and onwards). Some measures to prevent hypoglycemia-related mortality in rats include providing access to food soon after the injection, administration of glucose/sucrose solutions during the first 24-48 h after the injection, administration of STZ to fed animals, and using anomer-equilibrated solutions of STZ. Hyperglycemia-related mortality following injection of high doses of STZ can be overcome with insulin administration. In conclusion, STZ is a valuable chemical for inducing diabetes in rats, but some practical guides should be considered to perform well-conducted and ethical studies.
1 August 2016 in Journal of Food Composition and Analysis
Animal experimentation helps us to understand human biology. Rodents and, in particular, rats are among the most common animals used in animal experiments. Reporting data on animal age, animal body weight, and animal postnatal developmental stages is not consistent, which can cause the failure to translate animal data to humans. This review summarizes age-related postnatal developmental stages in rats by addressing age-related changes in their body weights. The age and body weight of animals can affect drug metabolism, gene expression, metabolic parameters, and other dependent variables measured in animal studies. In addition, considering the age and the body weight of the animals is of particular importance in animal modeling of human diseases. Appropriate reporting of age, body weight, and the developmental stage of animals used in studies can improve animal to human translation.