| HIV protease inhibitors induce metabolic dysfunction in part via increased JNK1/2 pro-inflammatory signaling in L6 cells. | |
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MedLine Citation:
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PMID: 21968131 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Protease inhibitors (PIs), such as atazanavir sulfate and ritonavir, are used clinically to prevent the progression of HIV and are known to induce insulin resistance. To determine whether PI-mediated insulin resistance is induced by activation of pro-inflammatory cascades, L6 skeletal muscle cells were treated ±atazanavir sulfate, ritonavir, or atazanavir sulfate+ritonavir, and ±insulin. Treatment with atazanavir sulfate, ritonavir, or atazanavir sulfate+ritonavir for 24 or 48h significantly increased basal glucose uptake (P<0.05) and atazanavir sulfate+ritonavir treatment increased basal glucose uptake significantly more than ritonavir or atazanavir sulfate treatment alone (P<0.05). Atazanavir sulfate+ritonavir treatment for 48h completely prevented insulin stimulation of glucose uptake (P>0.05). When compared to untreated cells, basal palmitate uptake and oxidation was found to be significantly higher in cells treated with PIs alone or in combination (P<0.05). Prior PI treatment alone or in combination prevented (P>0.05) the insulin-mediated increase in palmitate uptake and the insulin-mediated decrease in palmitate oxidation observed in the control group. Atazanavir sulfate treatment alone or in combination with ritonavir significantly increased JNK1/2 phosphorylation when compared to the control or ritonavir group (P<0.05) and this was accompanied by a rise (P<0.05) in AKT(Ser473) phosphorylation in the basal state. Total JNK1/2 and p38 MAPK protein content and p38 MAPK phosphorylation state were not altered in any of the treatment groups (P>0.05). Our data indicate that, in muscle cells, PIs induce metabolic dysfunction that is not limited to insulin-sensitive metabolism and that is potentially mediated by a rise in JNK1/2 pro-inflammatory signaling. |
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Authors:
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Lindsey D Bogachus; Lorraine P Turcotte |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-24 |
Journal Detail:
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Title: Antiviral research Volume: - ISSN: 1872-9096 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-10-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8109699 Medline TA: Antiviral Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier B.V. |
Affiliation:
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Department of Biological Sciences, Dana and David Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA, United States; Department of Kinesiology, Dana and David Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA, United States. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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