Abstract
Aim. Based on the previously established method, we developed a better and stable animal model of type 2 diabetes mellitus by high-fat diet combined with multiple low-dose STZ injections. Meanwhile, this new model was used to evaluate the antidiabetic effect of berberine. Method. Wistar male rats fed with regular chow for 4 weeks received vehicle (control groups), rats fed with high-fat diet for 4 weeks received different amounts of STZ once or twice by intraperitoneal injection (diabetic model groups), and diabetic rats were treated with berberine (100 mg/kg, berberine treatment group). Intraperitoneal glucose tolerance test and insulin tolerance test were carried out. Moreover, fasting blood glucose, fasting insulin, total cholesterol, and triglyceride were measured to evaluate the dynamic blood sugar and lipid metabolism. Result. The highest successful rate (100%) was observed in rats treated with a single injection of 45 mg/kg STZ, but the plasma insulin level of this particular group was significantly decreased, and ISI has no difference compared to control group. The successful rate of 30 mg/kg STZ twice injection group was significantly high (85%) and the rats in this group presented a typical characteristic of T2DM as insulin resistance, hyperglycemia, and blood lipid disorder. All these symptoms observed in the 30 mg/kg STZ twice injection group were recovered by the treatment of berberine. Conclusion. Together, these results indicated that high-fat diet combined with multiple low doses of STZ (30 mg/kg at weekly intervals for 2 weeks) proved to be a better way for developing a stable animal model of type 2 diabetes, and this new model may be suitable for pharmaceutical screening.
Highlights
There has been a tragic increase in diabetes across the world, paralleling the overweight and obesity epidemic
The purpose of the present study is to develop an appropriate, stable animal model which is analogous to the human type 2 diabetes mellitus through a combination of high-fat diet with multiple low-dose STZ injections
STZ was purchased from Sigma, insulin was purchased from Eli Lilly, Changchun, China; glucose, total cholesterol (TC), and triglyceride (TG) test kits were obtained from Beijing BHKT Clinical Reagent Co., Ltd, Beijing, China; iodine [125I]insulin radioimmunoassay kit was purchased from Tianjing Nine Tripods Medical & Bioengineering Co., Ltd, Tianjing, China; Other reagents were purchased from Beijing General Chemical Reagent Factory, Beijing, China
Summary
There has been a tragic increase in diabetes across the world, paralleling the overweight and obesity epidemic. It is great urgency to find better treatments and novel prevention strategies for type 2 diabetes. To accomplish this goal, appropriate experimental models are considered as essential tools for understanding the molecular basis, pathogenesis of the vascular and neural lesions, actions of therapeutic agents, and genetic or environmental influences that increase the risks of type 2 diabetes. There are numerous animal models (natural as well as developed) available for the study of type 2 diabetes [1,2,3,4], the pattern of disease establishment and progress in most of them did not appear to be similar to the clinical situation in humans. There is a continued quest among the investigators with respect to the establishment of better animal model for type 2 diabetes by adjusting the existing methods, developing new methodologies, or a combination of both
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