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Lipotoxicity is glucose-dependent in INS-1E cells but not in human islets and MIN6 cells

BACKGROUND: Prolonged elevated levels of lipids have negative effects on beta-cell function and mass (lipotoxicity). To what extent exposure to high glucose concentration is important in the harmful effects of lipids (glucolipotoxicity) has been debated. METHODS: We addressed beta-cell lipotoxicity...

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Autores principales: Sargsyan, Ernest, Bergsten, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141549/
https://www.ncbi.nlm.nih.gov/pubmed/21745359
http://dx.doi.org/10.1186/1476-511X-10-115
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author Sargsyan, Ernest
Bergsten, Peter
author_facet Sargsyan, Ernest
Bergsten, Peter
author_sort Sargsyan, Ernest
collection PubMed
description BACKGROUND: Prolonged elevated levels of lipids have negative effects on beta-cell function and mass (lipotoxicity). To what extent exposure to high glucose concentration is important in the harmful effects of lipids (glucolipotoxicity) has been debated. METHODS: We addressed beta-cell lipotoxicity by measuring apoptosis in isolated intact control human islets and insulin-secreting cell lines MIN6 and INS-1E cultured in the presence of palmitate and low (5.5 mM) or high (25 mM) glucose for 48 hours. RESULTS: In both cell lines and human islets palmitate induced apoptosis after culture at low glucose. Palmitate-induced apoptosis was not increased after culture at high compared to low glucose in human islets and MIN6 cells but glucose-induced rise in apoptosis was observed in INS-1E cells. The rise in apoptosis in INS-1E cells was partially reversed by inclusion of AMPK-agonist AICAR. When CPT1-inhibitor etomoxir was included during culture at low glucose palmitate-triggered apoptosis was accentuated both in the islets and the cell lines. Palmitate oxidation in human islets and the cell lines was comparable after culture at low glucose. At high glucose, palmitate oxidation was reduced by 30% in human islets and MIN6 cells but by 80% in INS-1E cells. In INS-1E cells, AICAR increased oxidation of palmitate. Presence of etomoxir at low glucose decreased palmitate oxidation both in the islets and the cell lines. CONCLUSIONS: In summary, lipotoxicity is evident not only in the presence of high but also low glucose concentrations. Additional effects of glucose are prominent in INS-1E but not in MIN6 cells and intact control human islets, which are able to efficiently oxidize fatty acids at high glucose and in this way avoid glucolipotoxicity.
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spelling pubmed-31415492011-07-23 Lipotoxicity is glucose-dependent in INS-1E cells but not in human islets and MIN6 cells Sargsyan, Ernest Bergsten, Peter Lipids Health Dis Research BACKGROUND: Prolonged elevated levels of lipids have negative effects on beta-cell function and mass (lipotoxicity). To what extent exposure to high glucose concentration is important in the harmful effects of lipids (glucolipotoxicity) has been debated. METHODS: We addressed beta-cell lipotoxicity by measuring apoptosis in isolated intact control human islets and insulin-secreting cell lines MIN6 and INS-1E cultured in the presence of palmitate and low (5.5 mM) or high (25 mM) glucose for 48 hours. RESULTS: In both cell lines and human islets palmitate induced apoptosis after culture at low glucose. Palmitate-induced apoptosis was not increased after culture at high compared to low glucose in human islets and MIN6 cells but glucose-induced rise in apoptosis was observed in INS-1E cells. The rise in apoptosis in INS-1E cells was partially reversed by inclusion of AMPK-agonist AICAR. When CPT1-inhibitor etomoxir was included during culture at low glucose palmitate-triggered apoptosis was accentuated both in the islets and the cell lines. Palmitate oxidation in human islets and the cell lines was comparable after culture at low glucose. At high glucose, palmitate oxidation was reduced by 30% in human islets and MIN6 cells but by 80% in INS-1E cells. In INS-1E cells, AICAR increased oxidation of palmitate. Presence of etomoxir at low glucose decreased palmitate oxidation both in the islets and the cell lines. CONCLUSIONS: In summary, lipotoxicity is evident not only in the presence of high but also low glucose concentrations. Additional effects of glucose are prominent in INS-1E but not in MIN6 cells and intact control human islets, which are able to efficiently oxidize fatty acids at high glucose and in this way avoid glucolipotoxicity. BioMed Central 2011-07-11 /pmc/articles/PMC3141549/ /pubmed/21745359 http://dx.doi.org/10.1186/1476-511X-10-115 Text en Copyright ©2011 Sargsyan and Bergsten; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Sargsyan, Ernest
Bergsten, Peter
Lipotoxicity is glucose-dependent in INS-1E cells but not in human islets and MIN6 cells
title Lipotoxicity is glucose-dependent in INS-1E cells but not in human islets and MIN6 cells
title_full Lipotoxicity is glucose-dependent in INS-1E cells but not in human islets and MIN6 cells
title_fullStr Lipotoxicity is glucose-dependent in INS-1E cells but not in human islets and MIN6 cells
title_full_unstemmed Lipotoxicity is glucose-dependent in INS-1E cells but not in human islets and MIN6 cells
title_short Lipotoxicity is glucose-dependent in INS-1E cells but not in human islets and MIN6 cells
title_sort lipotoxicity is glucose-dependent in ins-1e cells but not in human islets and min6 cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141549/
https://www.ncbi.nlm.nih.gov/pubmed/21745359
http://dx.doi.org/10.1186/1476-511X-10-115
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