| ObjectiveIn addition to the classic function of statins in reducing serum cholesterol level and cardiovascular morbidity and mortality, recent research has demonstrated that statins also play important roles in regulating glucose metabolism of diabetic patients. However, the potential effect of statin therapy to affect on glucose metabolism has been controversial. Therefore, in order to further clarify the effect of statins on the glucose metabolism, we studied the early induction of simvatatin in diabetic rats, analysis of simvastatin on the effect of fasting plasma glucose and serum insulin level in different stage of diabetic rats, and then investigate the effect of simvatatin on fasting plasma glucose in streptozotocin (STZ) induced diabetic rats.MethodsOne hundred male Wistar rats were fed with standard diet for one week and numbered according to the body weights, the rats were randomly divided into four groups, with25rats in each group. Group A:normal control rats (fed with standard diet), Group B:diabetic model rats (fed with high-fat diet), Group C:the early simvastatin induced diabetic rats (fed with high-fat diet), Group D:the late simvastatin induced diabetic rats (fed with high-fat diet). Group A rats received sodium citrate buffer (35mk/kg). Group B, Group C and Group D rats were injected with STZ (35mg/kg) after4weeks to induce type2diabetic model rats, Group B rats were received equivalent distilled water instead, Group C rats were received simvatatin (10mg/kg/day) at the beginning of the experiment, Group D rats were treated with simvatatin after successful induction of diabetes. The following parameters were assayed in each group during variance period:body weight (W), fasting plasma glucose (FPG), serum insulin level (Ins), total cholesterol (TC), triglyceride (TG) and high density lipoprotein cholesterol (HDL-C).The oral glucose tolerance test (OGTT) was performed to test the fasting plasma glucose and serum insulin levels, then the islet function was evaluated. Comparisons among multiple groups were achieved via one-way analysis of variance (ANOVA). SNK-q and Dunnett-t test were applied to compare probabilities of data between two groups.Results1. Fluid and food intake, body weight in each group:compared with normal control rats, there was statistically significant increased fluid and food intakes (p<0.05) and decreased bodyweight (p<0.05) in diabetic rats, the early simvastatin induced diabetic rats and the late simvastatin induced diabetic rats.2. Fasting plasma glucose and lipid profile in each group:compared with normal control rats, the levels of fasting plasma glucose (FPG), total cholesterol (TC) and triglyceride (TG) significant higher (p<0.05) and decreased in high density lipoprotein cholesterol (HDL-C) values (p<0.05). Compared with diabetic model rats, at the end of four weeks, the early simvastatin induced diabetic rats significantly decreased the total cholesterol (TC) and triglyceride (TG) values (p<0.05), increased the high density lipoprotein cholesterol (HDL-C) and fasting plasma glucose (FPG) levels (p<0.05) and easily induced type2diabetic model rats; at the end of eight weeks, the levels of fasting plasma glucose (FPG) were significantly increased (p<0.05) in both the early simvastatin induced diabetic rats and the late simvastatin induced diabetic rats, the late simvastatin induced diabetic rats decreased the total cholesterol (TC) and triglyceride (TG) values (p<0.05), increased the levels of high density lipoprotein cholesterol (HDL-C)(p<0.05).3. Difference of glucose and insulin profiles during OGTT in each group:the levels of glucose and insulin began to increase in30min after2g/Kg oral glucose and reached the peak in1hour, while the normal levels decreased in2hours in normal control rats. The glucose values were increased significantly in30min (p<0.05) and reached the peak in2hour in diabetic model rats, the insulin levels in diabetic rats were still lower than that of normal control rats. The early simvastatin induced diabetic rats showed significantly higher glucose values (p<0.05), the glucose levels reached the peak in2hours without the secretion of insulin peak (p<0.05). The glucose values got the peak in1hour (p<0.05), fell in2hour and there was no secretion of insulin peak in the late simvastatin induced diabetic rats.4. Difference of areas under the curve for glucose/insulin during OGTT in each group:the AUC(INS) values were lower in diabetic model rats, the early and late simvastatin induced diabetic rats than that of in normal control rats; while the AUC(GLU) values were higher in diabetic model rats, the early and late simvastatin induced diabetic rats than that of in normal control rats.Conclusions1. The rats, which fed with high fat diet, were injected with early simvastatin showed hyperglycemia by impairing the function of islet β cells and easily induced the type2diabetic model rats.2. The late simvastatin induced diabetic rats, which treated with simvastatin after successful induction of diabetes, can improve the lipid metabolism and increase the fasting plasma glucose values. |
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