Changes in mitochondrial carriers exhibit stress-specific signatures in INS-1Eβ-cells exposed to glucose versus fatty acids.

Chronic exposure of β-cells to metabolic stresses impairs their function and potentially induces apoptosis. Mitochondria play a central role in coupling glucose metabolism to insulin secretion. However, little is known on mitochondrial responses to specific stresses; i.e. low versus high glucose, sa...

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Autores principales:	Thierry Brun, Pasquale Scarcia, Ning Li, Pascale Gaudet, Dominique Duhamel, Ferdinando Palmieri, Pierre Maechler
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5659366b00e841df9705bd3d7d86ae48
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spelling	oai:doaj.org-article:5659366b00e841df9705bd3d7d86ae482021-11-18T08:42:14ZChanges in mitochondrial carriers exhibit stress-specific signatures in INS-1Eβ-cells exposed to glucose versus fatty acids.1932-620310.1371/journal.pone.0082364https://doaj.org/article/5659366b00e841df9705bd3d7d86ae482013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24349266/?tool=EBIhttps://doaj.org/toc/1932-6203Chronic exposure of β-cells to metabolic stresses impairs their function and potentially induces apoptosis. Mitochondria play a central role in coupling glucose metabolism to insulin secretion. However, little is known on mitochondrial responses to specific stresses; i.e. low versus high glucose, saturated versus unsaturated fatty acids, or oxidative stress. INS-1E cells were exposed for 3 days to 5.6 mM glucose, 25 mM glucose, 0.4 mM palmitate, and 0.4 mM oleate. Culture at standard 11.1 mM glucose served as no-stress control and transient oxidative stress (200 µM H2O2 for 10 min at day 0) served as positive stressful condition. Mito-array analyzed transcripts of 60 mitochondrion-associated genes with special focus on members of the Slc25 family. Transcripts of interest were evaluated at the protein level by immunoblotting. Bioinformatics analyzed the expression profiles to delineate comprehensive networks. Chronic exposure to the different metabolic stresses impaired glucose-stimulated insulin secretion; revealing glucotoxicity and lipo-dysfunction. Both saturated and unsaturated fatty acids increased expression of the carnitine/acylcarnitine carrier CAC, whereas the citrate carrier CIC and energy sensor SIRT1 were specifically upregulated by palmitate and oleate, respectively. High glucose upregulated CIC, the dicarboxylate carrier DIC and glutamate carrier GC1. Conversely, it reduced expression of energy sensors (AMPK, SIRT1, SIRT4), metabolic genes, transcription factor PDX1, and anti-apoptotic Bcl2. This was associated with caspase-3 cleavage and cell death. Expression levels of GC1 and SIRT4 exhibited positive and negative glucose dose-response, respectively. Expression profiles of energy sensors and mitochondrial carriers were selectively modified by the different conditions, exhibiting stress-specific signatures.Thierry BrunPasquale ScarciaNing LiPascale GaudetDominique DuhamelFerdinando PalmieriPierre MaechlerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e82364 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Thierry Brun Pasquale Scarcia Ning Li Pascale Gaudet Dominique Duhamel Ferdinando Palmieri Pierre Maechler Changes in mitochondrial carriers exhibit stress-specific signatures in INS-1Eβ-cells exposed to glucose versus fatty acids.
description	Chronic exposure of β-cells to metabolic stresses impairs their function and potentially induces apoptosis. Mitochondria play a central role in coupling glucose metabolism to insulin secretion. However, little is known on mitochondrial responses to specific stresses; i.e. low versus high glucose, saturated versus unsaturated fatty acids, or oxidative stress. INS-1E cells were exposed for 3 days to 5.6 mM glucose, 25 mM glucose, 0.4 mM palmitate, and 0.4 mM oleate. Culture at standard 11.1 mM glucose served as no-stress control and transient oxidative stress (200 µM H2O2 for 10 min at day 0) served as positive stressful condition. Mito-array analyzed transcripts of 60 mitochondrion-associated genes with special focus on members of the Slc25 family. Transcripts of interest were evaluated at the protein level by immunoblotting. Bioinformatics analyzed the expression profiles to delineate comprehensive networks. Chronic exposure to the different metabolic stresses impaired glucose-stimulated insulin secretion; revealing glucotoxicity and lipo-dysfunction. Both saturated and unsaturated fatty acids increased expression of the carnitine/acylcarnitine carrier CAC, whereas the citrate carrier CIC and energy sensor SIRT1 were specifically upregulated by palmitate and oleate, respectively. High glucose upregulated CIC, the dicarboxylate carrier DIC and glutamate carrier GC1. Conversely, it reduced expression of energy sensors (AMPK, SIRT1, SIRT4), metabolic genes, transcription factor PDX1, and anti-apoptotic Bcl2. This was associated with caspase-3 cleavage and cell death. Expression levels of GC1 and SIRT4 exhibited positive and negative glucose dose-response, respectively. Expression profiles of energy sensors and mitochondrial carriers were selectively modified by the different conditions, exhibiting stress-specific signatures.
format	article
author	Thierry Brun Pasquale Scarcia Ning Li Pascale Gaudet Dominique Duhamel Ferdinando Palmieri Pierre Maechler
author_facet	Thierry Brun Pasquale Scarcia Ning Li Pascale Gaudet Dominique Duhamel Ferdinando Palmieri Pierre Maechler
author_sort	Thierry Brun
title	Changes in mitochondrial carriers exhibit stress-specific signatures in INS-1Eβ-cells exposed to glucose versus fatty acids.
title_short	Changes in mitochondrial carriers exhibit stress-specific signatures in INS-1Eβ-cells exposed to glucose versus fatty acids.
title_full	Changes in mitochondrial carriers exhibit stress-specific signatures in INS-1Eβ-cells exposed to glucose versus fatty acids.
title_fullStr	Changes in mitochondrial carriers exhibit stress-specific signatures in INS-1Eβ-cells exposed to glucose versus fatty acids.
title_full_unstemmed	Changes in mitochondrial carriers exhibit stress-specific signatures in INS-1Eβ-cells exposed to glucose versus fatty acids.
title_sort	changes in mitochondrial carriers exhibit stress-specific signatures in ins-1eβ-cells exposed to glucose versus fatty acids.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/5659366b00e841df9705bd3d7d86ae48
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Changes in mitochondrial carriers exhibit stress-specific signatures in INS-1Eβ-cells exposed to glucose versus fatty acids.

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