摘要
目的选用2型糖尿病自发性模型Goto-Kakisaki(GK)大鼠为实验对象,在观察靶向过氧化物酶体增生物激活受体γ(PPARγ)激动剂吡格列酮对糖尿病治疗作用的基础上,检测其对肝组织糖异生过程重要参与分子表达水平的影响。方法将GK大鼠随机分为3组:模型对照组、吡格列酮10、5 mg/kg组,另设Wistar大鼠为正常对照组。大鼠连续灌胃给药14 d,并在给药前、给药期间及给药后动态测定大鼠血糖、体质量变化;给药结束后次日进行糖耐量实验,逆转录聚合酶链反应(reverse transcriptase-polymerase chain reaction,RT-PCR)测定PPARγ、磷酸烯醇丙酮酸羧激酶(PEPCK)、葡糖-6-磷酸(G6P)、果糖-1,6-二磷酸酶(FBP1)、小异二聚体伙伴分子(SHP)mRNA表达。结果给药第14天血糖结果显示,与模型对照组血糖值(18.84±1.83)mmol/L相比,吡格列酮10、5 mg/kg剂量组大鼠血糖明显下降(P<0.01),分别为(9.67±0.46)和(10.83±0.81)mmol/L;灌胃5%葡萄糖溶液120 min后,与模型组血糖值(11.4±1.0)mmol/L相比,吡格列酮10、5 mg/kg剂量组大鼠血糖明显下降(P<0.01),分别为(6.0±0.9)和(5.7±0.6)mmol/L,糖耐量水平增强。给药14 d后,与模型组相比,吡格列酮10、5 mg/kg组大鼠肝组织中PPARγ、SHP的mRNA表达增加,PEPCK、G6P、FBP1的mRNA表达降低。结论该研究揭示了PPARγ激动剂的降糖效应,其途径之一是通过抑制糖异生得以实现,而且提示SHP很可能介入了PPARγ调控糖异生的过程。
Objective To investigate the effect of pioglitazone,a peroxisome proliferator-activated receptor γ（ PPARγ） agonist,on the expression level of important molecules related to the process of gluconeogenesis in the liver.Methods GK rats were randomly divided into three groups： model control group,pioglitazone 10 and 5 mg / kg groups while Wistar rats were used as normal controls. Pioglitazone was orally administered to the rats for 14 days. The blood glucose levels and relative body mass of rats were measured before,during,and after administration. The next day after the14 days of administration of pioglitazone,glucose tolerance tests were performed,and the mRNA expression of PPARγ,phosphoenolpyruvate carboxylase kinase（ PEPCK）,glucose-6-phosphate（ G6P）,fructose-1,6-bisphosphatase（ FBP1）and small differences dimer partner molecules（ SHP） in rat livers was determined by RT-PCR. Results On the 14 th day of administration,the blood glucose levels [（ 9. 67 ± 0. 46） and（ 10. 83 ± 0. 81） mmol / L,respectively] of pioglitazone 10 and 5 mg / kg groups was significantly lower than that [（ 18. 84 ± 1. 83） mmol / L] of model control group（ P〈0. 01） 120 min after oral glucose intake（ 5% solution）,the blood glucose level [（ 6. 0 ± 0. 9） and（ 5. 7 ± 0. 6） mmol / L,respectively] of the pioglitazone 10 and 5 mg / kg groups was significantly lower than that [（ 11. 4 ± 1. 0） mmol / L]of model control group（ P〈0. 01）,suggesting the enhanced glucose tolerance in the pioglitazone groups. After 14 days of administration of pioglitazone,mRNA expression of PPARγ and SHP in the livers of pioglitazone groups increased,while mRNA expression of PEPCK,G6 P and FBP1 in the livers of pioglitazone groups decreased compared with the model group.Conclusion The hypoglycemic effect of PPARγ agonists can be achieved by inhibiting gluconeogenesis. SHP may play a role in the process of glucogenesis regulated by PPARγ.
出处
《军事医学》
CAS
CSCD
北大核心
2016年第5期370-373,共4页
Military Medical Sciences
基金
军事医学科学院创新基金(YC02016)
