Liver derived Extracellular Vesicles as Insulin Bait
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/52092 |
Resumo: | Tese de mestrado, Bioquímica (Bioquímica Médica) Universidade de Lisboa, Faculdade de Ciências, 2021 |
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Liver derived Extracellular Vesicles as Insulin Baitpré-diabetesresistência à insulinafígadovesiculas extracelularesrecetor de insulinaTeses de mestrado - 2021Departamento de Química e BioquímicaTese de mestrado, Bioquímica (Bioquímica Médica) Universidade de Lisboa, Faculdade de Ciências, 2021Obesity and diabetes are widely recognized as pandemic metabolic disorders of the 21st century due to sedentarism and caloric-unbalanced diets. However, there is a silver lining, prediabetes, which precedes diabetes and is characterized by hyperinsulinemia, is a reversible condition. Thus, the prediabetic stage should receive the proper attention. Being prediabetes a multi-systemic disorder, interorgan communication plays a critical role in the disease. Recently, one particular mean of inter-organ communication captured our attention: the extracellular vesicles (EVs), which are released by every cell in the body and transport specific cargo (proteins, DNA, microRNA, and lipids) along the bloodstream, triggering metabolic alteration in distant recipient cells. Interestingly, soluble insulin receptor (InsR) was identified in the systemic circulation. The current thesis aims at revealing a novel aspect of diabetes regulation, supporting a critical role for insulin bound to EVs in disease progression. In this work, it was discovered that in a prediabetic state, there is an increase of insulin receptors in the surface of liver-derived EVs, in relation to the healthy control group. Remarkably, the same does not happen in muscle-derived EVs. Moreover, these InsR harbouring EVs bind insulin in their surface and the liver-derived ones bind ten times more insulin than muscle EVs. It was observed that muscle cells uptake liver-derived EVs, and these EVs modulate glucose uptake. Notably, liver EVs, isolated from prediabetic animals, promote glucose uptake in muscle cells by 2-fold, as opposed to 1,2-fold of healthy EVs. This increase in glucose uptake is only observed when muscle cells are incubated with EVs for a prolonged time, strongly indicating that EVs induce a long-term response. Taken together, this thesis shows that the composition of liver EVs, in insulin and InsR, is modulated by the organismal metabolic state and thus the outcome of the communication between the EVs-producer and recipient cells. A particular focus was given on the communication between liver and muscle in the context of the prediabetic environment, and it was observed that prediabetic liver EVs are performing a compensatory effect by increasing glucose uptake. Our data raise the possibility that EVs harbouring InsR can be used as therapeutic tools in patients.Oliveira, Rita Machado deCarvalho, Margarida Henriques da Gama, 1972-Repositório da Universidade de LisboaRibeiro, Pedro Videira202120212024-11-30T00:00:00Z2021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10451/52092TID:202994597enginfo:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:57:10Zoai:repositorio.ul.pt:10451/52092Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:03:15.056104Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Liver derived Extracellular Vesicles as Insulin Bait |
title |
Liver derived Extracellular Vesicles as Insulin Bait |
spellingShingle |
Liver derived Extracellular Vesicles as Insulin Bait Ribeiro, Pedro Videira pré-diabetes resistência à insulina fígado vesiculas extracelulares recetor de insulina Teses de mestrado - 2021 Departamento de Química e Bioquímica |
title_short |
Liver derived Extracellular Vesicles as Insulin Bait |
title_full |
Liver derived Extracellular Vesicles as Insulin Bait |
title_fullStr |
Liver derived Extracellular Vesicles as Insulin Bait |
title_full_unstemmed |
Liver derived Extracellular Vesicles as Insulin Bait |
title_sort |
Liver derived Extracellular Vesicles as Insulin Bait |
author |
Ribeiro, Pedro Videira |
author_facet |
Ribeiro, Pedro Videira |
author_role |
author |
dc.contributor.none.fl_str_mv |
Oliveira, Rita Machado de Carvalho, Margarida Henriques da Gama, 1972- Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Ribeiro, Pedro Videira |
dc.subject.por.fl_str_mv |
pré-diabetes resistência à insulina fígado vesiculas extracelulares recetor de insulina Teses de mestrado - 2021 Departamento de Química e Bioquímica |
topic |
pré-diabetes resistência à insulina fígado vesiculas extracelulares recetor de insulina Teses de mestrado - 2021 Departamento de Química e Bioquímica |
description |
Tese de mestrado, Bioquímica (Bioquímica Médica) Universidade de Lisboa, Faculdade de Ciências, 2021 |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021 2021 2021-01-01T00:00:00Z 2024-11-30T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/52092 TID:202994597 |
url |
http://hdl.handle.net/10451/52092 |
identifier_str_mv |
TID:202994597 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/embargoedAccess |
eu_rights_str_mv |
embargoedAccess |
dc.format.none.fl_str_mv |
application/pdf |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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