格列本脲、二甲双胍对GDM小鼠糖代谢的影响

Impact of glibenclamide and metformin on glucose metabolism for mice with gestational diabetes mellitus

目的探讨格列本脲和二甲双胍对妊娠期糖尿病(GDM)小鼠产前、产后在葡萄糖代谢方面的影响。方法采用链脲佐菌素诱导C57BL/6J孕鼠建立GDM模型。除GDM对照外,分别给予长效胰岛素、格列本脲和二甲双胍治疗。怀孕的第1天定义为妊娠日(GD0),自GD0起,每2 d测定体质量和空腹血糖。在GD18,每组各取8只安乐死,然后收集肝脏,另8只孕鼠继续饲养等待自然分娩。产后1周,测定所有小鼠葡萄糖耐量实验(GTT)、胰岛素耐量实验(ITT)。产后5周,再测定所有小鼠GTT、ITT。然后将小鼠安乐死收集肝脏。分别检测肝脏中磷酸化蛋白激酶B(p-AKT)、磷酸化叉头转录因子O1(p-FoxO1)、葡萄糖-6-磷酸酶(G6Pase)、磷酸烯醇式丙酮酸激酶(PEPCK)等蛋白的水平。结果格列本脲和二甲双胍可分别降低GDM小鼠产前及产后1周空腹血糖(P<0.05)。与GDM对照相比,格列本脲和二甲双胍干预组肝脏中的p-AKT、p-FoxO1水平升高(P<0.05),而G6Pase、PEPCK分别降低(P<0.05)。然而,在产后5周,2种干预对GDM小鼠的影响消失。结论格列本脲或二甲双胍可改善GDM小鼠产前及产后1周葡萄糖耐量、胰岛素抵抗,但对产后5周小鼠的作用消失。

Objective To investigate the respective effects of glibenclamide and metformin on antenatal and postpartum glucose metabolism for gestational diabetes mellitus(GDM) mice. Methods Streptozotocin was used to stimulate C57 BL/6 J mice to develop GDM. In addition to GDM control, treatment was respectively given with long-acting insulin, glibenclamide and metformin. The first day of pregnancy was defined as gestational day(GD0), body weight and fasting blood glucose were measured every 2 days from GD0. On GD18, 8 dams in each group were euthanized to collect livers. The remaining 8 dams in each group were housed for natural delivery. After 1 week of post-partum, glucose tolerance test(GTT) and insulin tolerance test(ITT) were measured for all mice. After 5 weeks of post-partum, the GTT and ITT were measured for all mice. The mice were then euthanized to collect livers. The hepatic levels of phosphor-protein kinase B(p-AKT), phosphor-Forkhead box transcription factor O1(p-FoxO1), glucose-6-phosphatase(G6 Pase), phosphoenolpyruvate carboxykinase(PEPCK) were measured respectively. Results Glibenclamide and metformin could decrease fasting blood glucose respectively in GDM mice with antenatal and 1 week postpartum(P<0.05). Compared with the GDM control, p-AKT and p-FoxO1 levels increased(P<0.05) while G6 Pase and PEPCK reduced(P<0.05) respectively in livers from the glibenclamide and metformin intervened groups. However,after 5 weeks of post-partum,the effects of two interventions on the GDM mice disappeared. Conclusions Glibenclamide and metformin may improve the glucose tolerance and insulin resistance for GDM mice with antenatal and 1 week postpartum,but have poor effects on those with 5 weeks postpartum.