Placental inositol reduced in gestational diabetes as glucose alters inositol transporters and IMPA1 enzyme expression
| Autor: | Neha Sharma, Mohammed Omedul Islam, Reshma Appukuttan Pillai, Keith M. Godfrey, Anne H. Y. Chu, Rohan M. Lewis, Shiao Chan, Oliver C Watkins, Preben Selvam |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Blood Glucose Male medicine.medical_specialty endocrine system diseases Endocrinology Diabetes and Metabolism Placenta Clinical Biochemistry Glucose Transport Proteins Facilitative Down-Regulation Context (language use) Biology Biochemistry Sodium-Glucose Transport Proteins Article chemistry.chemical_compound Endocrinology Pregnancy Internal medicine medicine Humans Inositol Cells Cultured chemistry.chemical_classification Biochemistry (medical) Infant Newborn Gestational age nutritional and metabolic diseases Metabolism medicine.disease Phosphoric Monoester Hydrolases Gestational diabetes Diabetes Gestational medicine.anatomical_structure Enzyme Glucose chemistry Gene Expression Regulation Case-Control Studies Female Signal Transduction |
| Zdroj: | J Clin Endocrinol Metab |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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