Influencing Factors in the Development of Rat Model of Type 2 Diabetes Mellitus and Their Characteristics

Objective To evaluate the influencing factors and explore a better method of developing rat model of type 2 diabetes by high fat chow and low dose of streptozotocin(STZ) injection.Methods Forty-five male Sprague Dawley(SD) rats,aged 4 week-old,were randomly divided into three groups:(1) Normal control group(NC,n = 9),fed with a standard chow,(2) high-fat group(HF,n = 9),fed with high-fat chow,(3) diabetes mellitus group,induced by intraperitoneal injection(ip) of STZ after high-fat chow feeding.The diabetic group was further divided into 3 subgroups: The group A(n = 9) was induced by 4 weeks of high-fat chow feeding followed by 30 mg/kg of STZ injection.Group B(n = 9) was induced by 8 weeks of high-fat feeding followed by 20 mg/kg of STZ.Group C(n = 9) was induced by 8 weeks of high-fat feeding followed by 30 mg/kg of STZ.OGTT was performed for 3 times at 48 hours,2 weeks and 4 weeks after STZ injection.Fasting serum insulin level,total serum cholesterol(TC) and triglyceride(TG) were measured.Insulin mRNA was detected by RT-PCR.Morphologic changes of islet cells stained by immunohistochemistry were analyzed and quantified with a color image analyzer.Results In group C,the fasting blood glucose level increased prominently and its variation appeared as decreasing in the first week and then increasing closely to baseline level within 4 weeks.The morbidity of diabetes was 100%.However,the diabetic morbidity in group A and group B was only 55.6%(5/9) and 11.1%(1/9),respectively.Compared with HF group,insulin sensitivity was worsen markedly(P0.01),and the reduction of insulin content in β cells by 39.3%(P0.01),β cell mass by 79.2%(P0.01) and insulin mRNA expression in the pancreas by 19.2%(P0.01) were detected in group C.On the contrary,the α cells mass increased by almost 1-fold(P0.01).Conclusion Rat model of type 2 diabetes induced by 4 weeks of high-fat chow feeding and low dose STZ(30 mg/kg) injection presents high morbidity of diabetes and stable features.