Establishment of Type 2 Diabetes Mellitus Models Using High-Fat Diet and STZ in Bama Minipigs

Abstract BackgroundIn the past 20 years, the number of adults with diabetes has tripled. For most of the researches are often conducted in rodent T2DM models, and effective drugs developed have low clinical conversion efficiency. Therefore, it is urgent to establish a large animal model to explore the pathogenesis of T2DM and formulate disease prevention and control strategies. MethodsThis study was designed to establish and validate a T2DM model in minipigs with notable hyperglycemia using a high-fat diet and low-dose streptozotocin (STZ)，and examined the influence of STZ infusion time, the difference between a high-fat diet and a high-cholesterol and high-fat diet, and the atherosclerotic lesions accelerated by diabetes. Male Bama minipigs (n=24) were randomly divided into 5 groups; the control group was fed with normal diet for 9 months; STZ+HFD group and STZ+HCFD group were infused with 90 mg/kg STZ and then fed with a high-fat diet or high-cholesterol and high-fat diet for 9 months, respectively; HFD + STZ group and HCFD + STZ group were fed with a high-fat diet or high-cholesterol and high-fat diet, respectively, for nine months (after 3 months, pigs were injected with 90 mg/kg STZ intravenously). ResultsThe results showed the serum glucose concentrations were within the normal range in all groups except for HFD + STZ group and HCFD + STZ group. Animals fed with a high-fat diet for 9 months, did not develop apparent atherosclerotic lesions; nevertheless, atherosclerotic lesions were seen in animals fed with high-cholesterol and high-fat diets. Moreover, hyperglycemia accelerated atherosclerosis (lesions on the intimal surface of the abdominal aorta, 0.44±0.29 vs. 0.28±0.26) in minipigs. ConclusionsHigh-fat/high-cholesterol and high-fat diet combined with low-dose streptozotocin successfully established T2DM in minipigs. High-fat diet could not induce apparent atherosclerosis lesions but high-cholesterol and high-fat diet could during the nine months period. Hyperglycemia accelerated atherosclerosis in the minipigs.