关键词: 葡萄糖；胰岛β细胞；结节性硬化症-2基因；叉头转录因子-1基因；罗格列酮

Abstract:

Abstract: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 (5×10 cells /well) and cultivated for 48 h,then they were randomly divided into treatment groups containing different concentrations of glucose as ollows:5.6,7.8,11.1,16.7,22.2,and 27.6 mmol/L groups. After cultivated for 24 h,they were intervented by 10^-5 mmol/L  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 rosiglitazone the proliferation of pancreatic β cells (NIT-1 cell line) was found(P<0.05)and the apoptotic rate of cells was increased in a dose-dependent manner （1×10^-5 mol/L rosiglitazone group＞1×10^-6 mol/L rosiglitazone group＞1×10^-7 mol/L rosiglitazone group）.② When under same dose of glucose,the insulin secretion level in 11.1 mmol/L group was much higher than those in other groups(P<0.05),but the insulin secretion level was reduced  gradually following the decrease of glucose concentration(11.1 mmol/Lgroup＞16.7 mmol/L group＞22.5 mmol/L group＞27.6　mmol/L group).The insulin secretion level in 5.6 mol/L group was the lowest.③ After intervention of 10^-5 mol/L rosiglitazone,the expression levels of both FOXO1 and TSC2 mRNA were significantly lower   than those in control group (5.6 mmol/L group＜11.1 mmol/L  group＜16.7 mmol/L  group＜22.5 mmol/L  group＜ 27.6 mmol/L group).When the glucose concentration was over 16.7 mol/L,the expressions of  FOXO1 and TSC2 mRNA were obviously higher than those in the groups with glucose concentration ≤11.1 mmol/L after the intervention of 10-5 mol/L rosiglitazone.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.

Key words: glucose;pancreatic &beta, cells;tuberous sclerosis , complex2;forkhead box O1;rosiglitazone