Placental extracellular vesicles express active dipeptidyl peptidase IV; levels are increased in gestational diabetes mellitus. Issue 1 (1st December 2019)

• Record Type: Journal Article
• 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
• Is Part Of: Journal of extracellular vesicles. Volume 8:Issue 1(2019)
• Publication Date: 2019-12-01
• Subjects: Placental extracellular vesicles -- syncytiotrophoblast-derived extracellular vesicles -- gestational diabetes mellitus -- gliptin -- pregnancy -- dipeptidyl peptidase IV; Cells -- Mechanical properties -- Periodicals; Transport Vesicles; Cells -- Mechanical properties; Periodicals; Fulltext; Internet Resources; Periodicals; Electronic journals; Periodicals; 571.63
• DOI: 10.1080/20013078.2019.1617000
• Languages: English
• ISSNs: 2001-3078

Abstract

ABSTRACT: 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.