GDM progenies exhibit sex disparity in metabolism after respective therapies of insulin, glibenclamide and metformin in dams during pregnancy

Abstract

Background： The drug treatments for the pregnant women with gestational diabetes mellitus (GDM) have been concerned with their effects on both mothers and offspring. The aim of this study was to compare the intergenerational effects of insulin, glibenclamide and metformin on glucose and lipid metabolism in the offspring born to GDM mice. Methods: The murine GDM was induced by high fat diet. The offspring were grouped based on the treatments in maternal mice. ITT and GTT were performed at 4th week and 8th week of age, respectively. Serum levels of TC, TG, HDL-C and LDL-C plus hepatic levels of TG and TC, were respectively determined by enzymatic kits. Western blotting was conducted to detect related proteins in the livers from offspring. Results: The normalization of the dyslipidemia, hepatic lipid abnormality and insulin insensitivity elicited by the respective therapies of insulin, glibenclamide and metformin during maternal pregnancy still persisted in the male adult offspring. Specifically, the decreases in plasma TC, TG, LDL-C levels (29%, 37.8% and 57.7%, respectively, p˂0.05) and hepatic lipid contents (TC 31.3% and TG 39.2%, p˂0.05), the increases in hepatic phosphorylation levels of AKT, CPT1A ,PPAR- α and PPAR-γ (57.1%, 91.7% , 68% and 173.3%, respectively, p˂0.05) and the inhibition of G6Pase, PEPCK, HMGCS1 (35.7%, 68.8% and 77.3% respectively, p˂0.05) were still observed in the male offspring born to treated GDM mice from 4th to 8th week of age. Unexpectedly, the female progeny born to untreated GDM mice showed an autonomous recovery in glucose and lipid metabolism. Conclusions: Respective treatments in GDM mice during pregnancy with insulin, glibenclamide and metformin have the long-term persisted effects in male offspring, while female progenies born to untreated dams showed an autonomous inhibition of intergenerational relay of glucose and lipid dysregulation. Our current findings may shed a new light into GDM clinical practice.