Open AccessPlacental extracellular vesicles express active dipeptidyl peptidase IV; levels are increased in gestational diabetes mellitus
Author(s) -
Kandzija Neva,
Zhang Wei,
MottaMejia Carolina,
Mhlomi Vuyane,
McGowanDowney Jennifer,
James Tim,
Cerdeira Ana Sofia,
Tannetta Dionne,
Sargent Ian,
Redman Christopher W.,
Bastie Claire C.,
Vatish Manu
Publication year - 2019
Publication title -
journal of extracellular vesicles
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.94
H-Index - 68
ISSN - 2001-3078
DOI - 10.1080/20013078.2019.1617000
Subject(s) - vildagliptin , dipeptidyl peptidase 4 , gestational diabetes , dipeptidyl peptidase , placenta , endocrinology , medicine , diabetes mellitus , insulin , glucagon like peptide 1 , biology , intervillous space , pregnancy , fetus , metformin , type 2 diabetes , gestation , biochemistry , enzyme , genetics
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.