VMP1-related autophagy induced by a fructose-rich diet in B-cells: its prevention by incretins

Autores
Maiztegui, Barbara; Boggio, Veronica; Román, Carolina Lisi; Flores, Luis Emilio; del Zotto, Hector Herminio; Ropolo, Alejandro Javier; Grasso, Daniel Hector; Vaccaro, Maria Ines; Gagliardino, Juan Jose
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The aim of the present study was to demonstrate the role of autophagy and incretins inthe fructose-induced alteration of β-cell mass and function. Normal Wistar rats were fed(3 weeks) with a commercial diet without (C) or with 10% fructose in drinking water (F) aloneor plus sitagliptin (CS and FS) or exendin-4 (CE and FE). Serum levels of metabolic/endocrineparameters, B-cell mass, morphology/ultrastructure and apoptosis, vacuole membrane protein1 (VMP1) expression and glucose-stimulated insulin secretion (GSIS) were studied.Complementary to this, islets isolated from normal rats were cultured (3 days) without (C) orwith F and F + exendin-4 or chloroquine. Expression of autophagy-related proteins [VMP1and microtubule-associated protein light chain 3 (LC3)], apoptotic/antiapoptotic markers(caspase-3 and Bcl-2), GSIS and insulin mRNA levels were measured. F rats developed impairedglucose tolerance (IGT) and a significant increase in plasma triacylglycerols, thiobarbituricacid-reactive substances, insulin levels, homoeostasis model assessment (HOMA)for insulin resistance (HOMA-IR) and B-cell function (HOMA-B) indices. A significant reductionin B-cell mass was associated with an increased apoptotic rate and morphological/ultrastructuralchanges indicative of autophagic activity. All these changes were preventedby either sitagliptin or exendin-4. In cultured islets, F significantly enhanced insulinmRNA and GSIS, decreased Bcl-2 mRNA levels and increased caspase-3 expression.Chloroquine reduced these changes, suggesting the participation of autophagy in this process.Indeed, F induced the increase of both VMP1 expression and LC3-II, suggesting thatVMP1-related autophagy is activated in injured B-cells. Exendin-4 prevented islet-cell damageand autophagy development. VMP1-related autophagy is a reactive process againstF-induced islet dysfunction, being prevented by exendin-4 treatment. This knowledge couldhelp to use autophagy as a potential target for preventing progression from IGT to type 2diabetes mellitus.
Fil: Maiztegui, Barbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: Boggio, Veronica. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; Argentina
Fil: Román, Carolina Lisi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: Flores, Luis Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: del Zotto, Hector Herminio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: Ropolo, Alejandro Javier. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; Argentina
Fil: Grasso, Daniel Hector. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; Argentina
Fil: Vaccaro, Maria Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; Argentina
Fil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Materia
B-Cell Function
B-Cell Mass
Autophagy
Incretins
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/63859
Acceder
id CONICETDig_5582306daa34930567f25f94a9ec4327
oai_identifier_str oai:ri.conicet.gov.ar:11336/63859
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling VMP1-related autophagy induced by a fructose-rich diet in B-cells: its prevention by incretinsMaiztegui, BarbaraBoggio, VeronicaRomán, Carolina LisiFlores, Luis Emiliodel Zotto, Hector HerminioRopolo, Alejandro JavierGrasso, Daniel HectorVaccaro, Maria InesGagliardino, Juan JoseB-Cell FunctionB-Cell MassAutophagyIncretinshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The aim of the present study was to demonstrate the role of autophagy and incretins inthe fructose-induced alteration of β-cell mass and function. Normal Wistar rats were fed(3 weeks) with a commercial diet without (C) or with 10% fructose in drinking water (F) aloneor plus sitagliptin (CS and FS) or exendin-4 (CE and FE). Serum levels of metabolic/endocrineparameters, B-cell mass, morphology/ultrastructure and apoptosis, vacuole membrane protein1 (VMP1) expression and glucose-stimulated insulin secretion (GSIS) were studied.Complementary to this, islets isolated from normal rats were cultured (3 days) without (C) orwith F and F + exendin-4 or chloroquine. Expression of autophagy-related proteins [VMP1and microtubule-associated protein light chain 3 (LC3)], apoptotic/antiapoptotic markers(caspase-3 and Bcl-2), GSIS and insulin mRNA levels were measured. F rats developed impairedglucose tolerance (IGT) and a significant increase in plasma triacylglycerols, thiobarbituricacid-reactive substances, insulin levels, homoeostasis model assessment (HOMA)for insulin resistance (HOMA-IR) and B-cell function (HOMA-B) indices. A significant reductionin B-cell mass was associated with an increased apoptotic rate and morphological/ultrastructuralchanges indicative of autophagic activity. All these changes were preventedby either sitagliptin or exendin-4. In cultured islets, F significantly enhanced insulinmRNA and GSIS, decreased Bcl-2 mRNA levels and increased caspase-3 expression.Chloroquine reduced these changes, suggesting the participation of autophagy in this process.Indeed, F induced the increase of both VMP1 expression and LC3-II, suggesting thatVMP1-related autophagy is activated in injured B-cells. Exendin-4 prevented islet-cell damageand autophagy development. VMP1-related autophagy is a reactive process againstF-induced islet dysfunction, being prevented by exendin-4 treatment. This knowledge couldhelp to use autophagy as a potential target for preventing progression from IGT to type 2diabetes mellitus.Fil: Maiztegui, Barbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Boggio, Veronica. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; ArgentinaFil: Román, Carolina Lisi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Flores, Luis Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: del Zotto, Hector Herminio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Ropolo, Alejandro Javier. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; ArgentinaFil: Grasso, Daniel Hector. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; ArgentinaFil: Vaccaro, Maria Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; ArgentinaFil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaPortland Press2017-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/63859Maiztegui, Barbara; Boggio, Veronica; Román, Carolina Lisi; Flores, Luis Emilio; del Zotto, Hector Herminio; et al.; VMP1-related autophagy induced by a fructose-rich diet in B-cells: its prevention by incretins; Portland Press; Clinical Science; 131; 2-2017; 673-6870143-5221CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.clinsci.org/content/early/2017/02/10/CS20170010info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/ 10.1042/CS20170010info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-26T09:08:24Zoai:ri.conicet.gov.ar:11336/63859instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-11-26 09:08:25.263CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv VMP1-related autophagy induced by a fructose-rich diet in B-cells: its prevention by incretins
title VMP1-related autophagy induced by a fructose-rich diet in B-cells: its prevention by incretins
spellingShingle VMP1-related autophagy induced by a fructose-rich diet in B-cells: its prevention by incretins
Maiztegui, Barbara
B-Cell Function
B-Cell Mass
Autophagy
Incretins
title_short VMP1-related autophagy induced by a fructose-rich diet in B-cells: its prevention by incretins
title_full VMP1-related autophagy induced by a fructose-rich diet in B-cells: its prevention by incretins
title_fullStr VMP1-related autophagy induced by a fructose-rich diet in B-cells: its prevention by incretins
title_full_unstemmed VMP1-related autophagy induced by a fructose-rich diet in B-cells: its prevention by incretins
title_sort VMP1-related autophagy induced by a fructose-rich diet in B-cells: its prevention by incretins
dc.creator.none.fl_str_mv Maiztegui, Barbara
Boggio, Veronica
Román, Carolina Lisi
Flores, Luis Emilio
del Zotto, Hector Herminio
Ropolo, Alejandro Javier
Grasso, Daniel Hector
Vaccaro, Maria Ines
Gagliardino, Juan Jose
author Maiztegui, Barbara
author_facet Maiztegui, Barbara
Boggio, Veronica
Román, Carolina Lisi
Flores, Luis Emilio
del Zotto, Hector Herminio
Ropolo, Alejandro Javier
Grasso, Daniel Hector
Vaccaro, Maria Ines
Gagliardino, Juan Jose
author_role author
author2 Boggio, Veronica
Román, Carolina Lisi
Flores, Luis Emilio
del Zotto, Hector Herminio
Ropolo, Alejandro Javier
Grasso, Daniel Hector
Vaccaro, Maria Ines
Gagliardino, Juan Jose
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv B-Cell Function
B-Cell Mass
Autophagy
Incretins
topic B-Cell Function
B-Cell Mass
Autophagy
Incretins
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The aim of the present study was to demonstrate the role of autophagy and incretins inthe fructose-induced alteration of β-cell mass and function. Normal Wistar rats were fed(3 weeks) with a commercial diet without (C) or with 10% fructose in drinking water (F) aloneor plus sitagliptin (CS and FS) or exendin-4 (CE and FE). Serum levels of metabolic/endocrineparameters, B-cell mass, morphology/ultrastructure and apoptosis, vacuole membrane protein1 (VMP1) expression and glucose-stimulated insulin secretion (GSIS) were studied.Complementary to this, islets isolated from normal rats were cultured (3 days) without (C) orwith F and F + exendin-4 or chloroquine. Expression of autophagy-related proteins [VMP1and microtubule-associated protein light chain 3 (LC3)], apoptotic/antiapoptotic markers(caspase-3 and Bcl-2), GSIS and insulin mRNA levels were measured. F rats developed impairedglucose tolerance (IGT) and a significant increase in plasma triacylglycerols, thiobarbituricacid-reactive substances, insulin levels, homoeostasis model assessment (HOMA)for insulin resistance (HOMA-IR) and B-cell function (HOMA-B) indices. A significant reductionin B-cell mass was associated with an increased apoptotic rate and morphological/ultrastructuralchanges indicative of autophagic activity. All these changes were preventedby either sitagliptin or exendin-4. In cultured islets, F significantly enhanced insulinmRNA and GSIS, decreased Bcl-2 mRNA levels and increased caspase-3 expression.Chloroquine reduced these changes, suggesting the participation of autophagy in this process.Indeed, F induced the increase of both VMP1 expression and LC3-II, suggesting thatVMP1-related autophagy is activated in injured B-cells. Exendin-4 prevented islet-cell damageand autophagy development. VMP1-related autophagy is a reactive process againstF-induced islet dysfunction, being prevented by exendin-4 treatment. This knowledge couldhelp to use autophagy as a potential target for preventing progression from IGT to type 2diabetes mellitus.
Fil: Maiztegui, Barbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: Boggio, Veronica. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; Argentina
Fil: Román, Carolina Lisi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: Flores, Luis Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: del Zotto, Hector Herminio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: Ropolo, Alejandro Javier. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; Argentina
Fil: Grasso, Daniel Hector. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; Argentina
Fil: Vaccaro, Maria Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; Argentina
Fil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
description The aim of the present study was to demonstrate the role of autophagy and incretins inthe fructose-induced alteration of β-cell mass and function. Normal Wistar rats were fed(3 weeks) with a commercial diet without (C) or with 10% fructose in drinking water (F) aloneor plus sitagliptin (CS and FS) or exendin-4 (CE and FE). Serum levels of metabolic/endocrineparameters, B-cell mass, morphology/ultrastructure and apoptosis, vacuole membrane protein1 (VMP1) expression and glucose-stimulated insulin secretion (GSIS) were studied.Complementary to this, islets isolated from normal rats were cultured (3 days) without (C) orwith F and F + exendin-4 or chloroquine. Expression of autophagy-related proteins [VMP1and microtubule-associated protein light chain 3 (LC3)], apoptotic/antiapoptotic markers(caspase-3 and Bcl-2), GSIS and insulin mRNA levels were measured. F rats developed impairedglucose tolerance (IGT) and a significant increase in plasma triacylglycerols, thiobarbituricacid-reactive substances, insulin levels, homoeostasis model assessment (HOMA)for insulin resistance (HOMA-IR) and B-cell function (HOMA-B) indices. A significant reductionin B-cell mass was associated with an increased apoptotic rate and morphological/ultrastructuralchanges indicative of autophagic activity. All these changes were preventedby either sitagliptin or exendin-4. In cultured islets, F significantly enhanced insulinmRNA and GSIS, decreased Bcl-2 mRNA levels and increased caspase-3 expression.Chloroquine reduced these changes, suggesting the participation of autophagy in this process.Indeed, F induced the increase of both VMP1 expression and LC3-II, suggesting thatVMP1-related autophagy is activated in injured B-cells. Exendin-4 prevented islet-cell damageand autophagy development. VMP1-related autophagy is a reactive process againstF-induced islet dysfunction, being prevented by exendin-4 treatment. This knowledge couldhelp to use autophagy as a potential target for preventing progression from IGT to type 2diabetes mellitus.
publishDate 2017
dc.date.none.fl_str_mv 2017-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/63859
Maiztegui, Barbara; Boggio, Veronica; Román, Carolina Lisi; Flores, Luis Emilio; del Zotto, Hector Herminio; et al.; VMP1-related autophagy induced by a fructose-rich diet in B-cells: its prevention by incretins; Portland Press; Clinical Science; 131; 2-2017; 673-687
0143-5221
CONICET Digital
CONICET
url http://hdl.handle.net/11336/63859
identifier_str_mv Maiztegui, Barbara; Boggio, Veronica; Román, Carolina Lisi; Flores, Luis Emilio; del Zotto, Hector Herminio; et al.; VMP1-related autophagy induced by a fructose-rich diet in B-cells: its prevention by incretins; Portland Press; Clinical Science; 131; 2-2017; 673-687
0143-5221
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.clinsci.org/content/early/2017/02/10/CS20170010
info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/ 10.1042/CS20170010
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Portland Press
publisher.none.fl_str_mv Portland Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.011256

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