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Original investigation
GDM progenies exhibit sex disparity in metabolism after respective therapies of insulin, glibenclamide and metformin in dams during pregnancy
Keyang Chen
Anhui Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-3019-577X
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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.
Keywords
GDM, Offspring, Glibenclamide, Metformin, Glucose and lipid metabolism
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Fig.S The normalization of insulin sensitivity by the respective interventions of three drugs during maternal pregnancy was still maintained in male offspring at their adulthood A, The showed are the fasting plasma glucose in female offspring at 8 weeks of age in different groups. B, Plasma insulin levels were detected in female offspring at 8 weeks of age in different groups. C, HOMA-IR values were calculated in female offspring at 8 weeks of age in different groups. D, The demonstrated are the fasting plasma glucose in male offspring at 8 weeks of age in different groups. E, Plasma insulin levels were assayed in male offspring at 8 weeks of age in different groups. F, HOMA-IR levels were calculated in male offspring at 8 weeks of age in different groups. The values represent the mean ± SEM, n = 8-10 pups/group. The columns with different letters (a, b) are significantly different, P<0.05 (ANOVA, SNK).
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Original investigation
GDM progenies exhibit sex disparity in metabolism after respective therapies of insulin, glibenclamide and metformin in dams during pregnancy
Keyang Chen
Anhui Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-3019-577X
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 29 Sep, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7