Dataset Information

Placental endoplasmic reticulum stress in gestational diabetes: the potential for therapeutic intervention with chemical chaperones and antioxidants.

ABSTRACT:

Aims/hypothesis

The aim of this work was to determine whether placental endoplasmic reticulum (ER) stress may contribute to the pathophysiology of gestational diabetes mellitus (GDM) and to test the efficacy of chemical chaperones and antioxidant vitamins in ameliorating that stress in a trophoblast-like cell line in vitro.

Methods

Placental samples were obtained from women suffering from GDM and from normoglycaemic controls and were frozen immediately. Women with GDM had 2 h serum glucose levels > 9.0 mmol/l following a 75 g oral glucose tolerance test and were treated with diet and insulin when necessary. Western blotting was used to assess markers of ER stress. To test the effects of hyperglycaemia on the generation of ER stress, a new trophoblast-like cell line, BeWo-NG, was generated by culturing in a physiological glucose concentration of 5.5 mmol/l (over 20 passages) before challenging with 10 or 20 mmol/l glucose.

Results

All GDM patients were well-controlled (HbA1c 5.86?±?0.55% or 40.64?±?5.85 mmol/mol, n?=?11). Low-grade ER stress was observed in the placental samples, with dilation of ER cisternae and increased phosphorylation of eukaryotic initiation factor 2 subunit ?. Challenge of BeWo-NG with high glucose activated the same pathways, but this was as a result of acidosis of the culture medium rather than the glucose concentration per se. Addition of chemical chaperones 4-phenylbutyrate and tauroursodeoxycholic acid and vitamins C and E ameliorated the ER stress.

Conclusions/interpretation

This is the first report of placental ER stress in GDM patients. Chemical chaperones and antioxidant vitamins represent potential therapeutic interventions for GDM.

SUBMITTER: Yung HW

PROVIDER: S-EPMC5016560 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Publications

Placental endoplasmic reticulum stress in gestational diabetes: the potential for therapeutic intervention with chemical chaperones and antioxidants.

Yung Hong-Wa HW Alnæs-Katjavivi Patji P Jones Carolyn J P CJ El-Bacha Tatiana T Golic Michaela M Staff Anne-Cathrine AC Burton Graham J GJ

Diabetologia 20160712 10

<h4>Aims/hypothesis</h4>The aim of this work was to determine whether placental endoplasmic reticulum (ER) stress may contribute to the pathophysiology of gestational diabetes mellitus (GDM) and to test the efficacy of chemical chaperones and antioxidant vitamins in ameliorating that stress in a trophoblast-like cell line in vitro.<h4>Methods</h4>Placental samples were obtained from women suffering from GDM and from normoglycaemic controls and were frozen immediately. Women with GDM had 2 h seru ...[more]

PMID: 27406815

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Dataset Information

Placental endoplasmic reticulum stress in gestational diabetes: the potential for therapeutic intervention with chemical chaperones and antioxidants.

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Publications

Placental endoplasmic reticulum stress in gestational diabetes: the potential for therapeutic intervention with chemical chaperones and antioxidants.

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