Respective Interventions Of Insulin,Glibenclamide And Metformin In Gestational Diabetes Improved The Glucose And Lipid Metabolism In Offspring

Objective: Gestational Diabetes Mellitus(GDM)refers to a disease that causes abnormal glucose metabolism in pregnancy.in which the potential impaired glucose tolerance and insulin resistance are diagnosed during pregnancy.The aim of this study was to compare the respective effects of insulin,glybenclamide and metformin on glucose and lipid metabolism in the offspring born to Gestational diabetes mellitus(GDM)mice.Methods: C57 BL/6J Mice were kept under observation for one week to acclimatize the new conditions.Mice were maintained under a 12 h light–dark cycle at constant temperature(23 ± 2)? and relative humidity(50 ± 5)% with food and water available ad libitum.The pregnant mice were obtained by proesterous normal females being left for one night to copulate with the normal males(2:1).Onset of pregnancy was determined by the presence of a copulation plug,this day was considered as gestational day zero(GD0).The GDM mice were then developed by intraperitoneal injection of STZ at 40mg/kg on GD6,GD7,and GD8,respectively(within 48 h,glucose >11.1 mmol/L,defined as a successful model).The control pregnant mice were receiving an equal volume of citrate buffer.The pregnant mice were grouped as N:(normal control group),G:(GDM control group),GI:(GDM treated with insulin group),GG:(GDM treated with glybenclamide group),GM:(GDM treated with metformin group).ITT GTT were performed at 4 weeks and 8 weeks for all offspring,respectively.Plasma insulin was analyzed using an ELISA kit.Serum and hepatic levels of total TC,TG were respectively determined by enzymatic kits.Western blottingwas conducted to detect the insulin signaling pathway,glucose and lipid metabolism-related proteins in the livers from all offspring.Results: The normalization of the dyslipidemia,liver lipids and insulin sensitivity elicited by the respective therapies of insulin,glybenclamide and metformin during maternal pregnancy still persisted in the male offspring at 8 weeks old.Specifically,the improvements of TC,TG,LDL-C levels in plasma(P<0.05),hepatic lipid contents,the increase of G6 Pase,PEPCK,HMGCS1 level(P<0.05),and inhibition of hepatic phosphorylations of AKT,CPT1A(P<0.05)elicited by insulin,glybenclamide and metformin during maternal pregnancy were still observed in the male offspring from4 th to 8th week of age.While the normalization of those characteristics was only found in the female offspring with 4 weeks of age,and disappeared at their adulthood with 8weeks of age.Conclusions: Respective treatments in GDM mice during pregnancy with insulin,glybenclamide and metformin may be essential to increase insulin sensitivity,to lower blood lipid levels,and to improve glucose metabolism for male offspring even when they reach adulthood.While autorevoery of abnormal glucose and lipid metabolism caused by the GDM were seen in female adult offspring.Our findings may shed a new light into GDM clinical practice.