Glyburide treatment in gestational diabetes is associated with increased placental glucose transporter 1 expression and higher birth weight

Díaz, Paula; Dimasuay, Kris Genelyn; Koele-Schmidt, Lindsey; Jang, Brian; Barbour, Linda A.; Jansson, Thomas; Powell, Theresa L.

doi:10.1016/j.placenta.2017.05.016

Cited by 25 publications

(10 citation statements)

References 44 publications

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“…Varied levels of FATP expression have been reported in the placenta of GDM pregnancies [27,65]. The finding of unaltered FATP1, FATP2, FATP4, and FATP6 expression in trophoblasts exposed to GDM conditions suggest that changes solely to the glucose and insulin environment are unlikely to alter the expression of these transporters.…”

Section: Discussionmentioning

confidence: 98%

Elevated Glucose and Insulin Levels Decrease DHA Transfer across Human Trophoblasts via SIRT1-Dependent Mechanism

et al. 2020

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Gestational diabetes mellitus (GDM) results in reduced docosahexaenoic acid (DHA) transfer to the fetus, likely due to placental dysfunction. Sirtuin-1 (SIRT1) is a nutrient sensor and regulator of lipid metabolism. This study investigated whether the high glucose and insulin condition of GDM regulates DHA transfer and expression of fatty acid transporters and if this effect is related to SIRT1 expression and function. Syncytialized primary human trophoblasts were treated with and without glucose (25 mmol/L) and insulin (10−7 mol/L) for 72 h to mimic the insulin-resistance conditions of GDM pregnancies. In control conditions, DHA transfer across trophoblasts increased in a time- and dose-dependent manner. Exposure to GDM conditions significantly decreased DHA transfer, but increased triglyceride accumulation and fatty acid transporter expression (CD36, FABP3, and FABP4). GDM conditions significantly suppressed SIRT1 mRNA and protein expression. The SIRT1 inhibitor decreased DHA transfer across control trophoblasts, and recombinant SIRT1 and SIRT1 activators restored the decreased DHA transport induced by GDM conditions. The results demonstrate a novel role of SIRT1 in the regulation of DHA transfer across trophoblasts. The suppressed SIRT1 expression and the resultant decrease in placental DHA transfer caused by high glucose and insulin levels suggest new insights of molecular mechanisms linking GDM to fetal DHA deficiency.

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Section: Discussionmentioning

confidence: 98%

Elevated Glucose and Insulin Levels Decrease DHA Transfer across Human Trophoblasts via SIRT1-Dependent Mechanism

et al. 2020

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“…Evidently, the overexpression of placental TNF-α is associated with increased fetal adiposity (Radaelli et al 2003). Besides fetal adiposity, increased glucose transfer to the fetus causes fetal hyperglycaemia and fetal hyperinsulinaemia (Díaz et al 2017). Since the basal membrane GLUT-1 expression is regulated by insulinlike growth factor 1 (IGF1) (Baumann et al 2014), fetal hyperglycaemia may induce the secretion of fetal IGF1 which can regulate the expression of basal membrane GLUT-1 in a feedback loop manner.…”

Section: Placental Dysfunctionmentioning

confidence: 99%

Molecular pathways disrupted by gestational diabetes mellitus

Nguyen-Ngo

Jayabalan

Salomón

et al. 2019

Journal of Molecular Endocrinology

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Gestational diabetes mellitus (GDM) imposes serious short- and long-term health problems for mother and baby. An effective therapeutic that can reduce the incidence of GDM and improve long-term maternal and fetal outcomes is a major research priority, crucially important for public health. A lack of knowledge about the underlying pathophysiology of GDM has hampered the development of such therapeutics. What we do know, however, is that maternal insulin resistance, low-grade inflammation and endothelial cell dysfunction are three central features of pregnancies complicated by GDM. Indeed, data generated over the past decade have implicated a number of candidate regulators of insulin resistance, inflammation and endothelial cell dysfunction in placenta, maternal adipose tissue and skeletal muscle. These include nuclear factor-κB (NF-κB), peroxisome proliferator-activated receptors (PPARs), sirtuins (SIRTs), 5′ AMP-activated protein kinase (AMPK), glycogen synthase kinase 3 (GSK3), PI3K/mTOR, inflammasome and endoplasmic reticulum (ER) stress. In this review, the identification of these as key modulators of GDM will be discussed. The biochemical pathways involved in the formation of these may represent potential sites for intervention that may translate to therapeutic interventions to prevent the development of GDM.

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“…Recent data suggest that glyburide may also increase placental GLUT1 expression, which could augment fetal glucose delivery 95. Whether glyburide use increases the risk of fetal overgrowth independently of glycemic control is unclear, but LGA birth weight is thought to be a risk factor for adverse childhood metabolic outcomes 9697.…”

Section: Glyburidementioning

confidence: 99%

Novel therapies for diabetes mellitus in pregnancy

Feghali

Scifres

2018

BMJ

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Diabetes is a common complication of pregnancy, and the prevalence of all types of the disease is increasing worldwide. Diabetes in pregnancy is associated with short term and long term adverse effects for mother and child. The goal of treatment of diabetes in pregnancy is to minimize maternal and fetal adverse events related to hyperglycemia. Treatment options vary by type of diabetes, from a focus on lifestyle modifications in gestational diabetes to continuous glucose monitoring and insulin pumps in pregestational diabetes. Nevertheless, given the commonality of hyperglycemia, considerable overlap exists in the treatment of different types of diabetes in pregnancy. Also, despite ongoing research on treatment of diabetes in pregnancy for decades, changes in the characteristics of the patient population have highlighted the limited effectiveness of different therapies. Specifically, despite the co-occurrence of obesity and diabetes, treatment recommendations including glycemic targets are not altered in such cases and a single optimal treatment strategy for each type of diabetes in pregnancy does not seem to exist. Rather, the approach to treating pregnant women with diabetes likely needs to be individualized to maximize the short term and long term health of mother and child. This article will review recent clinical studies to summarize established treatment strategies and introduce novel therapies for diabetes in pregnancy.

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Glyburide treatment in gestational diabetes is associated with increased placental glucose transporter 1 expression and higher birth weight

Cited by 25 publications

References 44 publications

Elevated Glucose and Insulin Levels Decrease DHA Transfer across Human Trophoblasts via SIRT1-Dependent Mechanism

Elevated Glucose and Insulin Levels Decrease DHA Transfer across Human Trophoblasts via SIRT1-Dependent Mechanism

Molecular pathways disrupted by gestational diabetes mellitus

Novel therapies for diabetes mellitus in pregnancy

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