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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 treatment of diabetes mellitus in Goto-Kakisaki (GK) rats, a spontaneous model of type 2 diabetes. It plays an important role in the molecular expression of gluconeogenesis in liver tissues. Methods GK rats were randomly divided into 3 groups: model control group, pioglitazone 10,5 mg / kg group, another Wistar rats as normal control group. The rats were given gavage for 14 days. The blood glucose and body weight of the rats were measured before administration, during the administration and after administration, and the glucose tolerance test and the reverse transcription polymerase chain reaction (PEPCK), glucose-6-phosphate (G6P), fructose-1,6-bisphosphatase (FBP1) and small interfering RNA (PPARγ) were determined by reverse transcriptase-polymerase chain reaction Heterodimer partner molecule (SHP) mRNA expression. Results The blood glucose level on the 14th day of administration showed that compared with the blood glucose level of the model control group (18.84 ± 1.83) mmol / L, the blood glucose of the 10,5 mg / kg group of pioglitazone significantly decreased (P <0.01) 9.67 ± 0.46) and (10.83 ± 0.81) mmol / L, respectively. Compared with the model group (11.4 ± 1.0) mmol / L, the dose of pioglitazone 10,5 mg / kg The blood glucose of rats decreased significantly (P <0.01), (6.0 ± 0.9) and (5.7 ± 0.6) mmol / L respectively, and the level of glucose tolerance increased. At 14 days after administration, compared with the model group, the mRNA expressions of PPARγ and SHP increased and the mRNA expressions of PEPCK, G6P and FBP1 decreased in the liver of pioglitazone 10,5 mg / kg group. Conclusions This study reveals the hypoglycemic effects of PPARγ agonists. One of the ways to do this is through inhibition of gluconeogenesis, and suggests that SHP may be involved in the regulation of gluconeogenesis by PPARγ.