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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24349266/?tool=EBI |
| _version_ | 1828939895875305472 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T03:09:55Z |
| format | Article |
| id | doaj.art-5659366b00e841df9705bd3d7d86ae48 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T03:09:55Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5659366b00e841df9705bd3d7d86ae482022-12-21T23:19:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8236410.1371/journal.pone.0082364Changes in mitochondrial carriers exhibit stress-specific signatures in INS-1Eβ-cells exposed to glucose versus fatty acids.Thierry BrunPasquale ScarciaNing LiPascale GaudetDominique DuhamelFerdinando PalmieriPierre MaechlerChronic 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24349266/?tool=EBI |
| spellingShingle | 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. PLoS ONE |
| title | 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_short | 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 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24349266/?tool=EBI |
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