Adaptation of Sprague Dawley rats to long-term feeding of high fat or high fructose diets

Background: Present animal models used to emulate type 2 diabetes may not accurately reflect the metabolic changes that occur in humans. Aim of the study: The purpose of this research was to evaluate diets reported to induce insulin resistance and impaired glucose metabolism in rats as a potentially useful model for studying type 2 diabetes. Methods: Three groups of male Sprague Dawley rats (n=7) were fed either a control diet, based on AIN recommendations (53% cornstarch, 10% sucrose and 7% soybean oil), a high fat diet (25% soybean oil, 35% cornstarch) or a high fructose diet (53% fructose, 10% sucrose) for a 3 month period. Glucose tolerance tests were carried out in week 3 and week 9 of the experiment. At the termination of the experiment, serum insulin, glucose, cholesterol and triacylglycerols were measured. Glucose incorporation into glycogen and glycogen synthase activity were measured in soleus muscles. Results: Similar weight gain was observed for all three groups of rats. Glucose tolerance curves and fasting glucose levels were not significantly different at any time point in the experiment. Insulin levels were unchanged for the controls (171±21 pM), high fructose (164±16 pM) and high fat (181±30 pM) diets. Fasting serum triacylglycerols and cholesterol levels were not significantly elevated by dietary treatment. In soleus muscles, rats on all three diets had a significant increase in glycogen synthesis in response to insulin, but synthesis was similar in all three groups. Glycogen synthase activity was also not significantly affected by long-term dietary intervention. Conclusions: In this study, healthy Sprague Dawley rats fed high fat or high fructose diets for 3 months adapted to the nutritional intervention without developing classical signs of insulin resistance and impaired glucose tolerance.