Objective: To explore the influencing factors of establishing diabetes mellitus animal model by the combination of feeding high-fat diet for different periods of time and different dosage of streptozotocin (STZ).
Method: Eight-week-aged male Wistar rats were injected (i.p.) with 30 mg/kg STZ after high-fat diet being fed for 0, 4, 6 or 8 weeks respectively, and another 100 male rats were injected (i.p.) with 20 mg/kg, 30 mg/kg and 60 mg/kg STZ respectively after high-fat diet being fed for 4 weeks to establish diabetes mellitus models. Intraperitoneal glucose tolerance test and insulin tolerance test were carried out, and plasma indices were also measured. The type of models was verified by the administration (i.p.) of rosiglitazone.
Results: The successful rate of modeling in rats fed with high-fat diet for 4 weeks and received 30 mg/kg STZ injection (i.p.) was the highest (85% & 80%). Their plasma triglyceride and free fatty acid were increased significantly (P < 0.05), but the fasting plasma insulin was not different from the control group, these rats also presented impaired glucose tolerance and insulin resistance. The hyperglycemia and blood lipid disorders of these model rats were recovered by the treatment with rosiglitazone. With increasing age and the duration of high-fat diet, the death rate increased rapidly (50% & 65%). The successful rate of modeling at low dose of STZ (20 mg/kg, i.p.) was only 40%. The highest death rate (75%) was observed in rats treated with high dose of STZ (60 mg/kg, i.p.).
Conclusion: The duration of high-fat diet, the dosage of STZ and the age of rats were the most important factors for the successful rate and death rate while establishing diabetic animal model by the combination of high-fat diet and STZ.