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...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Taylor and Francis
2019
|
| _version_ | 1797055932222406656 |
|---|---|
| author | Kandzija, N Zhang, W Motta-Mejia, C Mhlomi, V McGowan-downey, J James, T Cerdeira, S Tannetta, D Sargent, I Redman, C Bastie, C Vatish, M |
| author_facet | Kandzija, N Zhang, W Motta-Mejia, C Mhlomi, V McGowan-downey, J James, T Cerdeira, S Tannetta, D Sargent, I Redman, C Bastie, C Vatish, M |
| author_sort | Kandzija, N |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T19:16:21Z |
| format | Journal article |
| id | oxford-uuid:188157fb-cbcf-4a71-a018-f3a5d3ec0537 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:16:21Z |
| publishDate | 2019 |
| publisher | Taylor and Francis |
| record_format | dspace |
| spelling | oxford-uuid:188157fb-cbcf-4a71-a018-f3a5d3ec05372022-03-26T10:43:42ZPlacental extracellular vesicles express active dipeptidyl peptidase IV; levels are increased in gestational diabetes mellitusJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:188157fb-cbcf-4a71-a018-f3a5d3ec0537EnglishSymplectic Elements at OxfordTaylor and Francis2019Kandzija, NZhang, WMotta-Mejia, CMhlomi, VMcGowan-downey, JJames, TCerdeira, STannetta, DSargent, IRedman, CBastie, CVatish, MGestational 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. |
| spellingShingle | Kandzija, N Zhang, W Motta-Mejia, C Mhlomi, V McGowan-downey, J James, T Cerdeira, S Tannetta, D Sargent, I Redman, C Bastie, C Vatish, M Placental extracellular vesicles express active dipeptidyl peptidase IV; levels are increased in gestational diabetes mellitus |
| title | Placental extracellular vesicles express active dipeptidyl peptidase IV; levels are increased in gestational diabetes mellitus |
| title_full | Placental extracellular vesicles express active dipeptidyl peptidase IV; levels are increased in gestational diabetes mellitus |
| title_fullStr | Placental extracellular vesicles express active dipeptidyl peptidase IV; levels are increased in gestational diabetes mellitus |
| title_full_unstemmed | Placental extracellular vesicles express active dipeptidyl peptidase IV; levels are increased in gestational diabetes mellitus |
| title_short | Placental extracellular vesicles express active dipeptidyl peptidase IV; levels are increased in gestational diabetes mellitus |
| title_sort | placental extracellular vesicles express active dipeptidyl peptidase iv levels are increased in gestational diabetes mellitus |
| work_keys_str_mv | AT kandzijan placentalextracellularvesiclesexpressactivedipeptidylpeptidaseivlevelsareincreasedingestationaldiabetesmellitus AT zhangw placentalextracellularvesiclesexpressactivedipeptidylpeptidaseivlevelsareincreasedingestationaldiabetesmellitus AT mottamejiac placentalextracellularvesiclesexpressactivedipeptidylpeptidaseivlevelsareincreasedingestationaldiabetesmellitus AT mhlomiv placentalextracellularvesiclesexpressactivedipeptidylpeptidaseivlevelsareincreasedingestationaldiabetesmellitus AT mcgowandowneyj placentalextracellularvesiclesexpressactivedipeptidylpeptidaseivlevelsareincreasedingestationaldiabetesmellitus AT jamest placentalextracellularvesiclesexpressactivedipeptidylpeptidaseivlevelsareincreasedingestationaldiabetesmellitus AT cerdeiras placentalextracellularvesiclesexpressactivedipeptidylpeptidaseivlevelsareincreasedingestationaldiabetesmellitus AT tannettad placentalextracellularvesiclesexpressactivedipeptidylpeptidaseivlevelsareincreasedingestationaldiabetesmellitus AT sargenti placentalextracellularvesiclesexpressactivedipeptidylpeptidaseivlevelsareincreasedingestationaldiabetesmellitus AT redmanc placentalextracellularvesiclesexpressactivedipeptidylpeptidaseivlevelsareincreasedingestationaldiabetesmellitus AT bastiec placentalextracellularvesiclesexpressactivedipeptidylpeptidaseivlevelsareincreasedingestationaldiabetesmellitus AT vatishm placentalextracellularvesiclesexpressactivedipeptidylpeptidaseivlevelsareincreasedingestationaldiabetesmellitus |