Placental extracellular vesicles express active dipeptidyl peptidase IV; levels are increased in gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy and is characterized by insulin resistance and decreased circulating glucagon-like peptide-1 (GLP-1). GDM resolves rapidly after delivery implicating the placenta in the disease. This study examines the biological...

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Published in:Journal of extracellular vesicles 2019-12, Vol.8 (1), p.1617000-n/a
Main Authors: Kandzija, Neva, Zhang, Wei, Motta-Mejia, Carolina, Mhlomi, Vuyane, McGowan-Downey, Jennifer, James, Tim, Cerdeira, Ana Sofia, Tannetta, Dionne, Sargent, Ian, Redman, Christopher W., Bastie, Claire C., Vatish, Manu
Format: Article
Language:English
Subjects:
Antibodies
Biological activity
Diabetes mellitus (non-insulin dependent)
Dipeptidyl-peptidase IV
Extracellular vesicles
Gestational diabetes
gestational diabetes mellitus
gliptin
Glucagon
Glucose
Hyperglycemia
Insulin resistance
Insulin secretion
Laboratories
Metabolic disorders
Nanoparticles
Peripheral blood
Physiology
Placenta
Placental extracellular vesicles
Pregnancy
Pregnancy complications
Proteins
syncytiotrophoblast-derived extracellular vesicles
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Summary:Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy and is characterized by insulin resistance and decreased circulating glucagon-like peptide-1 (GLP-1). GDM resolves rapidly after delivery implicating the placenta in the disease. This study examines the biological functions that cause this pathology. The placenta releases syncytiotrophoblast-derived extracellular vesicles (STB-EVs) into the maternal circulation, which is enhanced in GDM. Dipeptidyl peptidase IV (DPPIV) is known to play a role in type 2 diabetes by breaking down GLP-1, which in turn regulates glucose-dependent insulin secretion. STB-EVs from control and GDM women were analysed. We show that normal human placenta releases DPPIV-positive STB-EVs and that they are higher in uterine than paired peripheral blood, confirming placental origin. DPPIV-bound STB-EVs from normal perfused placentae are dose dependently inhibited with vildagliptin. DPPIV-bound STB-EVs from perfused placentae are able to breakdown GLP-1 in vitro. STB-EVs from GDM perfused placentae show greater DPPIV activity. Importantly, DPPIV-bound STB-EVs increase eightfold in the circulation of women with GDM. This is the first report of STB-EVs carrying a biologically active molecule that has the potential to regulate maternal insulin secretion.
ISSN:2001-3078
2001-3078
DOI:10.1080/20013078.2019.1617000