VMP1- Related autophagy induced by fructose rich diet in β-cells: its prevention by incretins

To demonstrate the role of autophagy and incretins on fructose‐induced alteration in β‐cell mass and function. Methods: Normal Wistar rats were fed (3 weeks) with commercial diet without (C) or with 10% fructose in drinking water (F) alone or plus sitagliptin (CS and FS) or exendin‐4 (CE and FE). Se...

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Autores principales: Maiztegui, Bárbara, Boggio, Verónica, Roman, Carolina Lisi, Flores, Luis Emilio, Del Zotto, Héctor Herminio, Ropolo, Alejandro, Grasso, Daniel Horacio, Vaccaro, María I., Gagliardino, Juan José
Formato: Articulo
Lenguaje:Inglés
Publicado: 2017
Materias:
Bioquímica
incretins
fructose-induced β-cell-injury
autophagy
β-cell mass
β-cell function
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/80683
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-80683
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Bioquímica
incretins
fructose-induced β-cell-injury
autophagy
β-cell mass
β-cell function
spellingShingle Bioquímica
incretins
fructose-induced β-cell-injury
autophagy
β-cell mass
β-cell function
Maiztegui, Bárbara
Boggio, Verónica
Roman, Carolina Lisi
Flores, Luis Emilio
Del Zotto, Héctor Herminio
Ropolo, Alejandro
Grasso, Daniel Horacio
Vaccaro, María I.
Gagliardino, Juan José
VMP1- Related autophagy induced by fructose rich diet in β-cells: its prevention by incretins
topic_facet Bioquímica
incretins
fructose-induced β-cell-injury
autophagy
β-cell mass
β-cell function
description To demonstrate the role of autophagy and incretins on fructose‐induced alteration in β‐cell mass and function. Methods: Normal Wistar rats were fed (3 weeks) with commercial diet without (C) or with 10% fructose in drinking water (F) alone or plus sitagliptin (CS and FS) or exendin‐4 (CE and FE). Serum levels of metabolic/endocrine parameters, β‐cell mass, morphology/ultrastructure and apoptosis, VMP1 expression and glucose‐stimulated insulin secretion (GSIS) were studied. Complementary, islets isolated from normal rats were cultured (3 days) without (C) or with F and F plus exendin‐4 (FE) or chloroquine (FCQ). Expression of autophagy related‐proteins (VMP1 and LC3), apoptotic/antiapoptotic markers (caspase‐3 and Bcl‐2), GSIS and insulin mRNA levels were measured. Results: F rats developed impaired glucose tolerance (IGT) and a significant increase in plasma triglyceride, TBARS, insulin levels, HOMAIR and HOMA‐β indexes. Significant β‐cell mass reduction was associated to an increased apoptotic rate and morphological/ultrastructural changes indicative of autophagic activity. All these changes were prevented by either sitagliptin or exendin‐4. In cultured islets, F significantly enhanced insulin mRNA and GSIS, decreased Bcl‐2 mRNA levels and increased caspase‐3 expression. Chloroquine reduced these changes suggesting autophagy participation in this process. Indeed, F induced the increase of both, VMP1 expression and LC3‐II, suggesting that VMP1‐related autophagy is activated in injured β‐cell. Exendin‐4 prevented islet‐cell damage and autophagy development. Conclusions: VMP1‐related autophagy is a reactive process against Finduced islet dysfunction, being prevented by exendin‐4 treatment. This knowledge could help to use autophagy as potential target for preventing progression from IGT toT2DM.
format Articulo
Articulo
author Maiztegui, Bárbara
Boggio, Verónica
Roman, Carolina Lisi
Flores, Luis Emilio
Del Zotto, Héctor Herminio
Ropolo, Alejandro
Grasso, Daniel Horacio
Vaccaro, María I.
Gagliardino, Juan José
author_facet Maiztegui, Bárbara
Boggio, Verónica
Roman, Carolina Lisi
Flores, Luis Emilio
Del Zotto, Héctor Herminio
Ropolo, Alejandro
Grasso, Daniel Horacio
Vaccaro, María I.
Gagliardino, Juan José
author_sort Maiztegui, Bárbara
title VMP1- Related autophagy induced by fructose rich diet in β-cells: its prevention by incretins
title_short VMP1- Related autophagy induced by fructose rich diet in β-cells: its prevention by incretins
title_full VMP1- Related autophagy induced by fructose rich diet in β-cells: its prevention by incretins
title_fullStr VMP1- Related autophagy induced by fructose rich diet in β-cells: its prevention by incretins
title_full_unstemmed VMP1- Related autophagy induced by fructose rich diet in β-cells: its prevention by incretins
title_sort vmp1- related autophagy induced by fructose rich diet in β-cells: its prevention by incretins
publishDate 2017
url http://sedici.unlp.edu.ar/handle/10915/80683
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