The objective is to create a female rat model which exhibits Non-Insulin Dependent Diabetes Mellitus (NIDDM). Literature supports that GMI's diabetic, fat male rat model is superior to other rat models in expressing similarities to human diabetes. Pancreatic insulin release, muscle insulin resistance, hyperglycemia and hyperlipidemia mimic the human condition. Significant growth in publications and use in research of the male (ZDF/Gmi-fa/fa) have occurred since the model's commercial availability. Phase I of GMI's research has demonstrated that the female ZDF can be induced to become diabetic through dietary manipulation. The response can be varied from normal glycemia and hyperinsulinemia to hyperglycemia and hypoinsulinemia. Phase II will seek to identify the synthetic defined diets and subcomponents which will provide the researcher with the ability to modulate the levels of glucose, insulin and lipids to best fulfill their needs. Experiments will be conducted to determine the model's sensitivity to insulin and response to antidiabetic drugs. Pancreatic histology will be done in experiment 1 and potentially in other selected groups of animals. Lastly the research plan will determine whether the diabetic response can be time induced, so that, older rats will yield response which more closely mimics the onset of NIDDM in humans.
This project will allow Genetic Models to market the first female model for NIDDM, allowing the research community to modulate the disease to understand the impact of new drug compounds, The ZDF obese female rat allows the researcher to create models ranging from normoglycemic and hyperinsulinemic, to full hyperglycemia and hypoinsulinemia, for studying NIDDM. Confirmation of anecdotal data is expected to establish this rat as a useful model for studying Syndrome X.
