Effects of rosiglitazone on expressions of FOXO1 and TSC2 gene and cell secretory function of NIT-1 cells after treated with high concentration glucose

Objective To study the effects of rosiglitazone on FOXO1 and TSC2 gene expressions,insulin secretory function,cell proliferation and apoptosis of pancreatic β cells under high concentration glucose condition.Methods The NIT-1 cells were put into plates(5×104 cells /well) and cultivated for 48 h,then they were randomly divided into treatment groups containing different concentrations of glucose as follows:5.6,7.8,11.1,16.7,22.2,and 27.6 mmol·L-1 groups.After cultivated for 24 h,they were intervented by 10-5 mmol·L-1 rosiglitazone for next 24 and 48 h,then the supernatant was collected.The insulin level was evaluated by radio-immunity technique,the cell proliferation and apoptosis were detected by immunofluorescence staining and MTT assay respectivly.The expressions of FOXO1 and TSC2 mRNA were detected by semi-quantitative RT-PCR assay.Results ① Under different concentrations of glucose,after treated with 10-6-10-5 mol·L-1 rosiglitazone the proliferation of pancreatic β cells(NIT-1 cell line) was found(P0.05)and the apoptotic rate of cells was increased in a dose-dependent manner(1×10-5 mol·L-1 rosiglitazone group1×10-6 mol·L-1 rosiglitazone group1×10-7 mol·L-1 rosiglitazone group).② When under same dose of glucose,the insulin secretion level in 11.1 mmol·L-1 group was much higher than those in other groups(P0.05),but the insulin secretion level was reduced gradually following the decrease of glucose concentration(11.1 mmol·L-1 group16.7 mmol·L-1 group22.5 mmol·L-1 group27.6 mmol·L-1 group).The insulin secretion level in 5.6 mmol·L-1 group was the lowest.③ After intervention of 10-5 mol·L-1rosiglitazone,the expression levels of both FOXO1 and TSC2 mRNA were significantly lower than those in control group(5.6 mmol·L-1 group11.1 mmol·L-1 group16.7 mmol·L-1 group22.5 mmol·L-1 group 27.6 mmol·L-1 group).When the glucose concentration was over 16.7 mmol·L-1,the expressions of FOXO1 and TSC2 mRNA were obviously higher than those in the groups with glucose concentration ≤11.1 mmol·L-1 after the intervention of 10-5mol·L-1rosiglitazone.Conclusion Rosiglitazone can improve the secretion function of pancreatic β cells and cell proliferation and alleviate insulin resistance by directly regulating FOXO1 and TSC2 expressions.