Liver derived Extracellular Vesicles as Insulin Bait

Detalhes bibliográficos
Autor(a) principal: Ribeiro, Pedro Videira
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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spelling 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
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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