孕期高脂肪饮食通过胰腺Pax6信号通路诱导孕鼠胰岛素抵抗的相关研究

High-fat diet during pregnancy induced maternal rats insulin resistance by pancreatic Pax6 signaling pathway

目的:研究孕期高脂肪饮食对孕鼠胰岛功能的影响和机制。方法:将30只孕鼠随机分为HF组与NC组(每组15只),分别摄取高热卡(高脂肪)及正常热卡饮食,孕期监测大鼠体重。孕鼠妊娠第20天禁食12h后测空腹血糖(FBG)、血清胰岛素(FINS)的水平,计算胰岛素敏感指数(ISI)及胰岛素抵抗指数(HOMA-IR),随即行口服葡萄糖耐量试验(OGTT)和胰岛素释放试验(IRT)。取血后处死孕鼠,即刻留取胰腺组织。RT-PCR和Real-time PCR法检测胰腺组织中配对盒因子6(Pax6)转录因子及其靶基因Pdx1,MafA和GLUT2的表达。结果:HF组大鼠妊娠期体重明显增加(P<0.05)。妊娠晚期,HF组孕鼠FBG显著高于NC组[(6.62±0.78)mmol/L vs(4.96±0.67)mmol/L,P<0.05],HOMA-IR显著高于NC组(1.64±0.29 vs 1.36±0.23,P<0.05)。OGTT和IRT结果显示,HF组孕鼠出现糖耐量受损及胰岛素抵抗;两组孕鼠FINS水平无显著差异。HF组孕鼠胰腺组织中Pax6转录因子及其靶基因Pdx1、MafA和GLUT2的表达均显著降低(P<0.05)。结论:孕期高脂肪饮食可能通过降低胰腺Pax6转录因子及其靶基因的表达诱导孕鼠发生糖耐量受损及胰岛素抵抗。

Objective：To explore the changes in islet function of maternal rats through consumption of high-fat diet during pregnancy and its mechanism. Methods：Thirty pregnant Wistar rats were randomly divided into 2 equal groups：high-fat-diet group, normal control group. Twenty days after gestation, fasting blood glucose concentration （FBG） and fasting serum insulin concentration（FINS） were measured. After that,oral glucose tolerance test（OGTT） and insulin release test（IRT） were performed in two groups. Then, these rats were killed ,and pancreas of both groups were taken immediately. Insulin sensitivity index （ISI） and insulin resistance index （HOMA-IR） were calculated according to FBG and FINS. RT-PCR and Real-time PCR were performed to detect the expression of paired box 6 （ Pax6 ） transcription factor and some of its target genes in pancreas tissue. Results：The body weight during pregnancy was significantly increased in the high-fat diet rats in comparison with normal control rats （P〈0.05）. The fasting plasma glucose of high-fat-diet rats was significantly increased in comparison with normal control rats [ （6.62±0.78）mmol/L vs （4.96 ±0.67 ） mmol/L, P 〈0.05 ） ] , while there was no significant difference in fasting serum insulin concentration of two groups. OGTT and IRT were abnormal in the high-fat diet rats. The high-fat diet rats were more prone to impaired glucose tolerance and insulin resistance. The level of the expression of Pax6 transcription factor and its target genes in pancreas, such as pancreatic and duodenal homeobox factor-1 （ Pdxl ）, vmar musculoaponeurotic fibrosarcoma oncogene homolog A （MafA） and glucose transporter 2 （GLUT2） were decreased significantly than those in NC group. Conclusion： High-fat diet during pregnancy may induced maternal rats insulin resistance by reducing pancreatic Pax6 and its target genes expression.