Short Interval Monitoring of Glucose in Zucker Diabetic Fatty ( ZDF ) Rats

Abstract

useful for studying disease pathophysiology and also for testing safety and effectiveness of potential treatments. One model of Type II diabetes is the Zucker diabetic fatty rat (ZDF/GmiTM). These rats have been developed by Genetic Models, INC of Indianapolis. Human Type II diabetes, also known as non-insulin dependent diabetes (NIDDM), is the most prevalent form of diabetes constituting about 80% of the diabetes cases. Its time of onset is during the middle to later years of life. It is often preceded by obesity, wide glycemic excursions often resulting in hypoglycemic episodes, and insulin resistance. There are about five million type II diabetics in the U.S. with a possible additional five million undiagnosed cases. The study of the pathophysiology of type II diabetes in rodents could have a significant effect on preventing or moderating the debilitating effects of the disease in the human population. The obese Zucker rat was first described in 1961 (1). These rats carried a recessive fa gene for obesity. They were insulin resistant, hyperinsulinemic and glucose intolerant but did not become frankly diabetic. In a colony of these rats maintained at Indiana University School of Medicine, some of the obese rats developed diabetes. These were initially described by Clark et. al. (2-4). The ZDF model was developed by selective inbreeding for the diabetic trait (5,6). The glucose levels of young obese male rats are normal. Between 7 and 10 weeks of age glucose levels rise sharply and then more gradually after 10 weeks of age. Female obese rats do not usually become diabetic, but diabetes can be induced by manipulation of dietary glucose and fat. The ZDF model is hypercholesterolemic and hypertriglyceidemic (6). Studies of the model have also shown some vascular changes in the retina and some changes in peripheral nerves. Studies on these diabetic rat models frequently involve monitoring glucose concentrations. The traditional method of obtaining a sample for measurement of glucose is to obtain blood from the tail by snipping the end of the tail. An alternative method would be to cannulate a jugular vein and maintain a heparinized vascular access. Both of these methods place limitations on the number of samples which can be collected and thus on the amount and frequency of data collected. Removing blood from the tail is painful and stressful to the animal. Stress can cause the release of stress hormones which may elevate glucose creating artifacts in the data. Vascular sampling is less stressful to the animal, but maintaining patent vascular access over long periods of time is difficult. Repeated vascular sampling also increases the probability of introducing a systemic infection. Because of the small size of rodents there is a limitation placed on the number of samples which can be obtained by the small blood volume. Repeated sampling can cause anemia and affect the general health of the animal. This can be partially alleviated in vascular access sampling by separating the plasma and returning the cells. Blood sampling for glucose measurement is also done during glucose tolerance tests to evaluate the progress or severity of the diabetes. During this test four or five samples may be taken to obtain the shape of the curve. There are some questions about the pathophysiology of this model which might be addressed by more frequent sampling of glucose. These include the basal insulin release patterns of Short Interval Monitoring of Glucose in Zucker Diabetic Fatty (ZDF) Rats

Cite this paper

@inproceedings{Janle2000ShortIM, title={Short Interval Monitoring of Glucose in Zucker Diabetic Fatty ( ZDF ) Rats}, author={Elsa M . Janle and Peter T . Kissinger}, year={2000} }