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Placental inositol reduced in gestational diabetes as glucose alters inositol transporters and IMPA1 enzyme expression

Placental inositol reduced in gestational diabetes as glucose alters inositol transporters and IMPA1 enzyme expression
Placental inositol reduced in gestational diabetes as glucose alters inositol transporters and IMPA1 enzyme expression
Context
Perturbed inositol physiology in insulin-resistant conditions has led to proposals of inositol supplementation for gestational diabetes (GDM) prevention, but placental inositol biology is poorly understood.

Objective
Investigate associations of maternal glycemia with placental inositol content, determine glucose effects on placental expression of inositol enzymes and transporters, and examine relations with birthweight.

Design and Participants
Case-control study of placentae from term singleton pregnancies (GDM n = 24, non-GDM n = 26), and culture of another 9 placentae in different concentrations of glucose and myo-inositol for 48 hours.

Main Outcome Measures
Placental inositol was quantified by the Megazyme assay. Relative expression of enzymes involved in myo-inositol metabolism and plasma membrane inositol transport was determined by quantitative RT-PCR and immunoblotting. Linear regression analyses were adjusted for maternal age, body mass index, ethnicity, gestational age, and sex.

Results
Placental inositol content was 17% lower in GDM compared with non-GDM. Higher maternal mid-gestation glycemia were associated with lower placental inositol. Increasing fasting glycemia was associated with lower protein levels of the myo-inositol synthesis enzyme, IMPA1, and the inositol transporters, SLC5A11 and SLC2A13, the expression of which also correlated with placental inositol content. In vitro, higher glucose concentrations reduced IMPA1 and SLC5A11 mRNA expression. Increasing fasting glycemia positively associated with customized birthweight percentile as expected in cases with low placental inositol, but this association was attenuated with high placental inositol.

Conclusion
Glycemia-induced dysregulation of placental inositol synthesis and transport may be implicated in reduced placental inositol content in GDM, and this may in turn be permissive to accelerated fetal growth.
0021-972X
e875–e890
Pillai, Reshma Appukuttan
c6a8a2d9-eaa1-4963-8c2c-5aed5d7e0503
Islam, Mohammed Omedul
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Selvam, Preben
989ffd8a-e214-43b5-a3ce-a814fc491ee7
Sharma, Neha
c5c663b2-86e4-4e3c-8f56-c28351419587
Chu, Anne HY
b47cf1e6-4e6c-4102-92c7-db21f1933c91
Watkins, Oliver C.
985df9b8-72d6-4f32-9ee3-54553c990fdc
Godfrey, Keith
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Lewis, Rohan
caaeb97d-ea69-4f7b-8adb-5fa25e2d3502
Chan, Shiao-Yng
3c9d8970-2cc4-430a-86a7-96f6029a5293
Pillai, Reshma Appukuttan
c6a8a2d9-eaa1-4963-8c2c-5aed5d7e0503
Islam, Mohammed Omedul
15ef9293-6460-405f-8c04-40d14a9d3f5e
Selvam, Preben
989ffd8a-e214-43b5-a3ce-a814fc491ee7
Sharma, Neha
c5c663b2-86e4-4e3c-8f56-c28351419587
Chu, Anne HY
b47cf1e6-4e6c-4102-92c7-db21f1933c91
Watkins, Oliver C.
985df9b8-72d6-4f32-9ee3-54553c990fdc
Godfrey, Keith
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Lewis, Rohan
caaeb97d-ea69-4f7b-8adb-5fa25e2d3502
Chan, Shiao-Yng
3c9d8970-2cc4-430a-86a7-96f6029a5293

Pillai, Reshma Appukuttan, Islam, Mohammed Omedul, Selvam, Preben, Sharma, Neha, Chu, Anne HY, Watkins, Oliver C., Godfrey, Keith, Lewis, Rohan and Chan, Shiao-Yng (2020) Placental inositol reduced in gestational diabetes as glucose alters inositol transporters and IMPA1 enzyme expression. Journal of Clinical Endocrinology & Metabolism, 106 (2), e875–e890. (doi:10.1210/clinem/dgaa814).

Record type: Article

Abstract

Context
Perturbed inositol physiology in insulin-resistant conditions has led to proposals of inositol supplementation for gestational diabetes (GDM) prevention, but placental inositol biology is poorly understood.

Objective
Investigate associations of maternal glycemia with placental inositol content, determine glucose effects on placental expression of inositol enzymes and transporters, and examine relations with birthweight.

Design and Participants
Case-control study of placentae from term singleton pregnancies (GDM n = 24, non-GDM n = 26), and culture of another 9 placentae in different concentrations of glucose and myo-inositol for 48 hours.

Main Outcome Measures
Placental inositol was quantified by the Megazyme assay. Relative expression of enzymes involved in myo-inositol metabolism and plasma membrane inositol transport was determined by quantitative RT-PCR and immunoblotting. Linear regression analyses were adjusted for maternal age, body mass index, ethnicity, gestational age, and sex.

Results
Placental inositol content was 17% lower in GDM compared with non-GDM. Higher maternal mid-gestation glycemia were associated with lower placental inositol. Increasing fasting glycemia was associated with lower protein levels of the myo-inositol synthesis enzyme, IMPA1, and the inositol transporters, SLC5A11 and SLC2A13, the expression of which also correlated with placental inositol content. In vitro, higher glucose concentrations reduced IMPA1 and SLC5A11 mRNA expression. Increasing fasting glycemia positively associated with customized birthweight percentile as expected in cases with low placental inositol, but this association was attenuated with high placental inositol.

Conclusion
Glycemia-induced dysregulation of placental inositol synthesis and transport may be implicated in reduced placental inositol content in GDM, and this may in turn be permissive to accelerated fetal growth.

Text
JCEM v2 submitted revised clean 2 - Accepted Manuscript
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More information

Accepted/In Press date: 30 October 2020
e-pub ahead of print date: 9 November 2020
Published date: 15 November 2020

Identifiers

Local EPrints ID: 444941
URI: http://eprints.soton.ac.uk/id/eprint/444941
ISSN: 0021-972X
PURE UUID: 85fb749f-9f2f-49b1-91dc-86d7f515b4ae
ORCID for Keith Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for Rohan Lewis: ORCID iD orcid.org/0000-0003-4044-9104

Catalogue record

Date deposited: 12 Nov 2020 17:33
Last modified: 23 Jul 2022 05:01

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Contributors

Author: Reshma Appukuttan Pillai
Author: Mohammed Omedul Islam
Author: Preben Selvam
Author: Neha Sharma
Author: Anne HY Chu
Author: Oliver C. Watkins
Author: Keith Godfrey ORCID iD
Author: Rohan Lewis ORCID iD
Author: Shiao-Yng Chan

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