| Fatty acids suppress autophagic turnover in {beta}-cells. | |
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MedLine Citation:
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PMID: 21859708 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Recent studies have shown that autophagy is essential for proper β-cell function and survival. However, it is yet unclear under what pathogenic conditions autophagy is inhibited in β-cells. Here we report that long term exposure to fatty acids and glucose block autophagic flux in β-cells, contributing to their toxic effect. INS1 cells expressing GFP-LC3 (an autophagosome marker) were treated with 0.4mM palmitate, 0.4mM oleate and various concentrations of glucose for 22h. Kinetics of the effect of fatty acids on autophagy showed a bi-phasic response. During the second phase of autophagy the size of autophagosomes and the content of autophagosome substrates (GFP-LC3, p62), and endogenous LC3 was increased. During the same phase, fatty acids suppressed autophagic degradation of long-lived protein in both INS1 cells and islets. In INS1 cells palmitate induced a 3 fold decrease in the number and the acidity of acidic vesicular organelles. This decrease was associated with a suppression of hydrolase activity, suppression of endocytosis and suppression of oxidative phosphorylation. The combination of fatty acids with glucose synergistically suppressed autophagic turnover, concomitantly suppressing insulin secretion. Rapamycin treatment resulted in partial reversal of the inhibition of autophagic flux, the inhibition of insulin secretion, and of the increase in cell death. Our results indicate that excess nutrient could impair autophagy in the long term, hence contributing to nutrient induced β-cell dysfunction. This may provide a novel mechanism that connects diet induced obesity and diabetes. |
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Authors:
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Guy Las; Sam Sereda; Jakob D Wikstrom; Gilad Twig; Orian S Shirihai |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-21 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Boston University School of Medicine, United States. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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