ABSTRACT
Wistar fatty rat was the first rat model of obese Type 2 diabetes (NIDDM) established on the basis of the hypothesis that both an environmental factor and genetic backgroud for diabetes were needed to develop diabetes (Ikeda et al., 1981). Among the environmental factors, obesity is assumed to be the most powerful risk factors related to metabolic and hormonal abnormalities. In respect of metabolism, the diabetogenic effect of obesity is of special interest, because obesity increases the insulin requirement and decreases the insulin sensitivity in the muscle, adipose tissue and liver. In fact, Type 2 diabetes is characterized by insulin resistance frequently associated with obesity in humans and animals. Zucker fatty rat develops obesity with
hyperinsulinemia, hyperlipidemia, hyperphagia, and glucose intolerance (Zucker and Antoniades, 1972). However, their blood glucose level is close to normal throughout their life. This suggested that additional factors were required to provoke diabetes in obesity. Therefore, the crossbreeding of the fa-gene carrier of Zucker rat with the Wistar Kyoto rat was started because the Wistar Kyoto rat is less sensitive to insulin and less tolerant to glucose than the Zucker rat. At the 5th generation of backcrossing, male obese hybrids, Wistar fatty rats, were found to be hyperglycemic in addition to hyperlipidemic and hyperinsulinemic, in association with severe obesity. These characteristics have been maintained through the later generations of backcrossing. The characteristics of Wistar fatty rats as compared
Table 1 Diabetes and obesity in male Zucker fatty (ZF) and male Wistar fatty (WF) rats at the age of 12-16 week.
