| ObjectiveGestational diabetes mellitus(GDM)is defined as the first glucose intolerance during pregnancy.GDM has short-and long-term influence on pregnant women and offspring.Treatment options for GDM are limited except for insulin.Recently,glibenclamide and metformin have been shown significant promise to treat GDM clinically,but the long-term effects of using these drugs during pregnancy remain poorly understood.Taking insulin as a control,this study was carried out to investigate the respective effects of glibenclamide and metformin on antenatal and postpartum outcomes for GDM mice.MethodsThe C57BL/6J(8 weeks old)female mice(17-20 g)and male mice(20-24 g)were placed in a cage at a ratio of 2:1 overnight.The mating was confirmed the next morning by examining the vaginal mucus plug,defined as the day of pregnancy(GD)0.The total of successful mating was 80 over the same period,among which 64 dams were administered with streptozotocin(STZ)to create GDM models,while the remaining 16 dams served as normal controls(N).The GDM mouse model was established by single intraperitoneal injection of STZ on each of GD6,GD7 and GD8 at a dose of 40 mg / kg / day,respectively,to ensure getting successful.At the same time period,normal control mice were intraperitoneally injected with 0.9% saline.When the fasting blood glucose concentration of the model group mice exceeded 11.1 mmol/l(200 mg/dl),the diabetic state of the mice was confirmed,that is,the GDM mouse model was confirmed to be successful.After successful modeling,in addition to the GDM controls(G),long-acting insulin was injected subcutaneously for animals in the insulin-treated group(GI),glibenclamide and metformin were given through gavage for animals in the glibenclamide-treated group(GG)and the metformin-treated group(GM).The weight and fasting blood glucose were measured every 2 days from GD0.On GD18,8 dams of each group were euthanized to be killed.The remaining 8 dams in each group were housed until giving birth naturally.The weight and fasting blood glucose were measured every 1 week.At week post-partum,GTT,ITT were measured for all mice and the blood was collected.At 5 weeks post-partum,the GTT and ITT were measured for all mice,and the blood was collected.The mice were then euthanized to be killed,the blood and liver were then collected.Serum lipids(TC,TG,LDL-C and HDL-C),liver lipids(TC,TG)and the hepatic levels of AKT,Fox O1,ACC,ACL,p-AKT,p-Fox O1,p-ACC,p-ACL,G6 Pase,PEPCK,SREBP2,HMGCS1 were measured respectively.ResultsCompared with GDM controls,Insulin,glibenclamide and metformin may significantly improve placental diameter,weight and dead fetus in GDM mice,while glibenclamide and metformin did not reduce the number of fetuses absorbed compared with insulin.Insulin,glibenclamide and metformin may substantially improve glucose tolerance,insulin resistance in GDM mice during pregnancy,and decrease maternal body weight,glucose,TC,TG,and LDL-C levels in serum,while the level of HDL-C was increased significantly.1 week postpartum,the effects(GTT,ITT)of these drugs significantly persisted,but slightly weakened.5 weeks postpartum,these effects disappeared and all the parameters in intervened groups became the same as those in GDM control group.In addition,p-AKT,p-Fox O1,p-ACC levels were increased,while G6 Pase,PEPCK,SREBP2 were reduced respectively in livers from all the intervened groups compared with the GDM control.However,after 5 weeks of post-partum,the effects of three separate interventions on the GDM mice disappeared.ConclusionsInsulin,glibenclamide and metformin may significantly improve the glucose tolerance,insulin resistance,and reduce body weight and blood lipid levels for GDM mice with antenatal and 1 week postpartum,but have poor long-term effects on those with 5 weeks postpartum.More importantly,metformin intervention may increase the number of absorbed fetuses for GDM mice compared with other interventions. |
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